Skip to main content
SpringerLink
Log in
Book cover

Human Fertility pp 39–73Cite as

Genetics of Female Infertility Due to Anomalies of the Ovary and Mullerian Ducts

  • Protocol
  • First Online:

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1154))

Abstract

Genetic factors are pivotal in reproductive development and subsequent reproductive processes. If disturbed, infertility can occur. In the female, genetic factors affecting the ovary and the uterus are not uncommon causes of infertility. Terminal deletions on the X long arm and X short arm and X chromosomal mosaicism have long been accepted as causes of premature ovarian failure (POF). Responsible genes on the X have not yet elucidated. Attractive candidate genes for POF also exist on autosomes, and in over a dozen genes molecular perturbations are documented in non-syndromic POF. The most common single-gene cause of POF is premutation carriers for FMR1 (fragile X syndrome). As other candidate genes and additional ethnic groups are interrogated, the proportion of POF cases due to single-gene mutation will increase. Among uterine anomalies, incomplete mullerian fusion is most common. Increased recurrence risks for first-degree relatives confirm a role for genetic factors; interrogation of candidate genes is under way.

This is a preview of subscription content, log in via an institution.

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Simpson JL (2012) Disorders of the gonads, genital tract and genitalia, 6th edn. Churchill-Livingstone, New York, NY

    Google Scholar 

  2. Jost A (1966) Problems of fetal endocrinology: the adrenal glands. Recent Prog Horm Res 22:541–574

    PubMed  CAS  Google Scholar 

  3. Schlessinger D, Garcia-Ortiz JE, Forabosco A, Uda M, Crisponi L, Pelosi E (2010) Determination and stability of gonadal sex. J Androl 31:16–25

    PubMed Central  PubMed  CAS  Google Scholar 

  4. Uhlenhaut NH, Jakob S, Anlag K, Eisenberger T, Sekido R, Kress J, Treier AC, Klugmann C, Klasen C, Holter NI, Riethmacher D, Schutz G, Cooney AJ, Lovell-Badge R, Treier M (2009) Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation. Cell 139:1130–1142

    PubMed  CAS  Google Scholar 

  5. Fraccaro M, Maraschio P, Pasquali F, Scappaticci S (1977) Women heterozygous for deficiency of the (p21 leads to pter) region of the X chromosome are fertile. Hum Genet 39:283–292

    PubMed  CAS  Google Scholar 

  6. Simpson JL (1986) Phenotypic-karyotypic correlations of gonadal determinants: current status and relationship to molecular studies. In: Sperling KVF (ed) Seventh international congress on human genetics. Springer, Berlin, pp 224–232

    Google Scholar 

  7. Simpson JL (1989) Genetic heterogeneity in XY sex reversal. Potential pitfalls in isolating the testis-determining-factor (TDF). In: Wachtel S (ed) Evolutionary mechanisms in sex determination. CRC, Baton Rouge, LA

    Google Scholar 

  8. Simpson JL (1988) Genetics of sex determination. In: Iizuka R, Semm K, Ohno T (eds) Human reproduction: current status, future prospect. Proceedings of VIth World Congress on Human Reproduction. Elsevier Science, Amsterdam

    Google Scholar 

  9. Simpson JL, Elias S (2003) Genetics in obstetrics and gynecology, 3rd edn. WB Saunders, Philadelphia

    Google Scholar 

  10. Simpson JL, Lebeau MM (1981) Gonadal and statural determinants on the X chromosome and their relationship to in vitro studies showing prolonged cell cycles in 45, X; 46, X, del(X)(p11); 46, X, del(X)(q13); and 46, X, del(X)(q22) fibroblasts. Am J Obstet Gynecol 141:930–940

    PubMed  CAS  Google Scholar 

  11. Ogata T, Matsuo N (1995) Turner syndrome and female sex chromosome aberrations: deduction of the principal factors involved in the development of clinical features. Hum Genet 95:607–629

    PubMed  CAS  Google Scholar 

  12. Simpson JL (2000) Genetic programming in ovarian development and oogenesis. In: Lobo RA, Kelsey J, Marcus R (eds) Menopause biology and pathobiology. Academic, London

    Google Scholar 

  13. Simpson JL, Rajkovic A (1999) Ovarian differentiation and gonadal failure. Am J Med Genet 89:186–200

    PubMed  CAS  Google Scholar 

  14. Fitch N, de Saint Victor J, Richer CL, Pinsky L, Sitahal S (1982) Premature menopause due to a small deletion in the long arm of the X chromosome: a report of three cases and a review. Am J Obstet Gynecol 142:968–972

    PubMed  CAS  Google Scholar 

  15. Krauss CM, Turksoy RN, Atkins L, McLaughlin C, Brown LG, Page DC (1987) Familial premature ovarian failure due to an interstitial deletion of the long arm of the X chromosome. N Engl J Med 317:125–131

    PubMed  CAS  Google Scholar 

  16. Tharapel AT, Anderson KP, Simpson JL, Martens PR, Wilroy RS Jr, Llerena JC Jr, Schwartz CE (1993) Deletion (X)(q26.1→q28) in a proband and her mother: molecular characterization and phenotypic-karyotypic deductions. Am J Hum Genet 52:463–471

    PubMed Central  PubMed  CAS  Google Scholar 

  17. Matzuk MM, Lamb DJ (2008) The biology of infertility: research advances and clinical challenges. Nat Med 14:1197–1213

    PubMed Central  PubMed  CAS  Google Scholar 

  18. Ochalski ME, Engle N, Wakim A, Ravnan BJ, Hoffner L, Rajkovic A, Surti U (2011) Complex X chromosome rearrangement delineated by array comparative genome hybridization in a woman with premature ovarian insufficiency. Fertil Steril 95(2433):e2439–2415

    Google Scholar 

  19. Kok HS, van Asselt KM, van der Schouw YT, Peeters PH, Wijmenga C (2005) Genetic studies to identify genes underlying menopausal age. Hum Reprod Update 11:483–493

    PubMed  CAS  Google Scholar 

  20. Stolk L, Zhai G, van Meurs JB, Verbiest MM, Visser JA, Estrada K, Rivadeneira F, Williams FM, Cherkas L, Deloukas P, Soranzo N, de Keyzer JJ, Pop VJ, Lips P, Lebrun CE, van der Schouw YT, Grobbee DE, Witteman J, Hofman A, Pols HA, Laven JS, Spector TD, Uitterlinden AG (2009) Loci at chromosomes 13, 19 and 20 influence age at natural menopause. Nat Genet 41:645–647

    PubMed Central  PubMed  CAS  Google Scholar 

  21. Christin-Maitre S, Tachdjian G (2010) Genome-wide association study and premature ovarian failure. Ann Endocrinol (Paris) 71:218–221

    CAS  Google Scholar 

  22. He C, Kraft P, Chen C, Buring JE, Pare G, Hankinson SE, Chanock SJ, Ridker PM, Hunter DJ, Chasman DI (2009) Genome-wide association studies identify loci associated with age at menarche and age at natural menopause. Nat Genet 41:724–728

    PubMed Central  PubMed  CAS  Google Scholar 

  23. Murray A, Bennett CE, Perry JR, Weedon MN, Jacobs PA, Morris DH, Orr N, Schoemaker MJ, Jones M, Ashworth A, Swerdlow AJ (2011) Common genetic variants are significant risk factors for early menopause: results from the Breakthrough Generations Study. Hum Mol Genet 20:186–192

    PubMed Central  PubMed  CAS  Google Scholar 

  24. Knauff EA, Franke L, van Es MA, van den Berg LH, van der Schouw YT, Laven JS, Lambalk CB, Hoek A, Goverde AJ, Christin-Maitre S, Hsueh AJ, Wijmenga C, Fauser BC (2009) Genome-wide association study in premature ovarian failure patients suggests ADAMTS19 as a possible candidate gene. Hum Reprod 24:2372–2378

    PubMed  CAS  Google Scholar 

  25. Knauff EA, Blauw HM, Pearson PL, Kok K, Wijmenga C, Veldink JH, van den Berg LH, Bouchard P, Fauser BC, Franke L (2011) Copy number variants on the X chromosome in women with primary ovarian insufficiency. Fertil Steril 95(1584–1588):e1581

    Google Scholar 

  26. Dudding TE, Lawrence O, Winship I, Froyen G, Vandewalle J, Scott R, Shelling AN (2010) Array comparative genomic hybridization for the detection of submicroscopic copy number variations of the X chromosome in women with premature ovarian failure. Hum Reprod 25:3159–3160, author reply 3160–3151

    PubMed  CAS  Google Scholar 

  27. Aboura A, Dupas C, Tachdjian G, Portnoi MF, Bourcigaux N, Dewailly D, Frydman R, Fauser B, Ronci-Chaix N, Donadille B, Bouchard P, Christin-Maitre S (2009) Array comparative genomic hybridization profiling analysis reveals deoxyribonucleic acid copy number variations associated with premature ovarian failure. J Clin Endocrinol Metab 94:4540–4546

    PubMed  CAS  Google Scholar 

  28. Quilter CR, Karcanias AC, Bagga MR, Duncan S, Murray A, Conway GS, Sargent CA, Affara NA (2010) Analysis of X chromosome genomic DNA sequence copy number variation associated with premature ovarian failure (POF). Hum Reprod 25:2139–2150

    PubMed  CAS  Google Scholar 

  29. Jones MH, Furlong RA, Burkin H, Chalmers IJ, Brown GM, Khwaja O, Affara NA (1996) The Drosophila developmental gene fat facets has a human homologue in Xp11.4 which escapes X-inactivation and has related sequences on Yq11.2. Hum Mol Genet 5:1695–1701

    PubMed  CAS  Google Scholar 

  30. Luoh SW, Bain PA, Polakiewicz RD, Goodheart ML, Gardner H, Jaenisch R, Page DC (1997) Zfx mutation results in small animal size and reduced germ cell number in male and female mice. Development 124:2275–2284

    PubMed  CAS  Google Scholar 

  31. Hanrahan JP, Gregan SM, Mulsant P, Mullen M, Davis GH, Powell R, Galloway SM (2004) Mutations in the genes for oocyte-derived growth factors GDF9 and BMP15 are associated with both increased ovulation rate and sterility in Cambridge and Belclare sheep (Ovis aries). Biol Reprod 70:900–909

    PubMed  CAS  Google Scholar 

  32. Dube JL, Wang P, Elvin J, Lyons KM, Celeste AJ, Matzuk MM (1998) The bone morphogenetic protein 15 gene is X-linked and expressed in oocytes. Mol Endocrinol 12:1809–1817

    PubMed  CAS  Google Scholar 

  33. Hanevik HI, Hilmarsen HT, Skjelbred CF, Tanbo T, Kahn JA (2011) A single nucleotide polymorphism in BMP15 is associated with high response to ovarian stimulation. Reprod Biomed Online 23:97–104

    PubMed  CAS  Google Scholar 

  34. Di Pasquale E, Beck-Peccoz P, Persani L (2004) Hypergonadotropic ovarian failure associated with an inherited mutation of human bone morphogenetic protein-15 (BMP15) gene. Am J Hum Genet 75:106–111

    PubMed Central  PubMed  Google Scholar 

  35. Dixit H, Rao LK, Padmalatha VV, Kanakavalli M, Deenadayal M, Gupta N, Chakrabarty B, Singh L (2006) Missense mutations in the BMP15 gene are associated with ovarian failure. Hum Genet 119:408–415

    PubMed  CAS  Google Scholar 

  36. Laissue P, Christin-Maitre S, Touraine P, Kuttenn F, Ritvos O, Aittomaki K, Bourcigaux N, Jacquesson L, Bouchard P, Frydman R, Dewailly D, Reyss AC, Jeffery L, Bachelot A, Massin N, Fellous M, Veitia RA (2006) Mutations and sequence variants in GDF9 and BMP15 in patients with premature ovarian failure. Eur J Endocrinol 154:739–744

    PubMed  CAS  Google Scholar 

  37. Zhang P, Shi YH, Wang LC, Chen ZJ (2007) Sequence variants in exons of the BMP-15 gene in Chinese patients with premature ovarian failure. Acta Obstet Gynecol Scand 86:585–589

    PubMed  CAS  Google Scholar 

  38. Ellison JW, Wardak Z, Young MF, Gehron Robey P, Laig-Webster M, Chiong W (1997) PHOG, a candidate gene for involvement in the short stature of Turner syndrome. Hum Mol Genet 6:1341–1347

    PubMed  CAS  Google Scholar 

  39. Rao E, Weiss B, Fukami M, Rump A, Niesler B, Mertz A, Muroya K, Binder G, Kirsch S, Winkelmann M, Nordsiek G, Heinrich U, Breuning MH, Ranke MB, Rosenthal A, Ogata T, Rappold GA (1997) Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome. Nat Genet 16:54–63

    PubMed  CAS  Google Scholar 

  40. Belin V, Cusin V, Viot G, Girlich D, Toutain A, Moncla A, Vekemans M, Le Merrer M, Munnich A, Cormier-Daire V (1998) SHOX mutations in dyschondrosteosis (Leri-Weill syndrome). Nat Genet 19:67–69

    PubMed  CAS  Google Scholar 

  41. Shears DJ, Vassal HJ, Goodman FR, Palmer RW, Reardon W, Superti-Furga A, Scambler PJ, Winter RM (1998) Mutation and deletion of the pseudoautosomal gene SHOX cause Leri-Weill dyschondrosteosis. Nat Genet 19:70–73

    PubMed  CAS  Google Scholar 

  42. Tachdjian G, Aboura A, Portnoi MF, Pasquier M, Bourcigaux N, Simon T, Rousseau G, Finkel L, Benkhalifa M, Christin-Maitre S (2008) Cryptic Xp duplication including the SHOX gene in a woman with 46, X, del(X)(q21.31) and premature ovarian failure. Hum Reprod 23:222–226

    PubMed  CAS  Google Scholar 

  43. Castrillon DH, Wasserman SA (1994) Diaphanous is required for cytokinesis in Drosophila and shares domains of similarity with the products of the limb deformity gene. Development 120:3367–3377

    PubMed  CAS  Google Scholar 

  44. Bione S, Sala C, Manzini C, Arrigo G, Zuffardi O, Banfi S, Borsani G, Jonveaux P, Philippe C, Zuccotti M, Ballabio A, Toniolo D (1998) A human homologue of the Drosophila melanogaster diaphanous gene is disrupted in a patient with premature ovarian failure: evidence for conserved function in oogenesis and implications for human sterility. Am J Hum Genet 62:533–541

    PubMed Central  PubMed  CAS  Google Scholar 

  45. Mumm S, Herrera L, Waeltz PW, Scardovi A, Nagaraja R, Esposito T, Schlessinger D, Rocchi M, Forabosco A (2001) X/autosomal translocations in the Xq critical region associated with premature ovarian failure fall within and outside genes. Genomics 76:30–36

    PubMed  CAS  Google Scholar 

  46. Prueitt RL, Chen H, Barnes RI, Zinn AR (2002) Most X;autosome translocations associated with premature ovarian failure do not interrupt X-linked genes. Cytogenet Genome Res 97:32–38

    PubMed  CAS  Google Scholar 

  47. Riva P, Magnani I, Fuhrmann Conti AM, Gelli D, Sala C, Toniolo D, Larizza L (1996) FISH characterization of the Xq21 breakpoint in a translocation carrier with premature ovarian failure. Clin Genet 50:267–269

    PubMed  CAS  Google Scholar 

  48. Lacombe A, Lee H, Zahed L, Choucair M, Muller JM, Nelson SF, Salameh W, Vilain E (2006) Disruption of POF1B binding to nonmuscle actin filaments is associated with premature ovarian failure. Am J Hum Genet 79:113–119

    PubMed Central  PubMed  CAS  Google Scholar 

  49. Bione S, Rizzolio F, Sala C, Ricotti R, Goegan M, Manzini MC, Battaglia R, Marozzi A, Vegetti W, Dalpra L, Crosignani PG, Ginelli E, Nappi R, Bernabini S, Bruni V, Torricelli F, Zuffardi O, Toniolo D (2004) Mutation analysis of two candidate genes for premature ovarian failure, DACH2 and POF1B. Hum Reprod 19:2759–2766

    PubMed  CAS  Google Scholar 

  50. Padovano V, Lucibello I, Alari V, Della Mina P, Crespi A, Ferrari I, Recagni M, Lattuada D, Righi M, Toniolo D, Villa A, Pietrini G (2011) The POF1B candidate gene for premature ovarian failure regulates epithelial polarity. J Cell Sci 124:3356–3368

    PubMed  CAS  Google Scholar 

  51. Katsuya T, Horiuchi M, Minami S, Koike G, Santoro NF, Hsueh AJ, Dzau VJ (1997) Genomic organization and polymorphism of human angiotensin II type 2 receptor: no evidence for its gene mutation in two families of human premature ovarian failure syndrome. Mol Cell Endocrinol 127:221–228

    PubMed  CAS  Google Scholar 

  52. Bione S, Toniolo D (2000) X chromosome genes and premature ovarian failure. Semin Reprod Med 18:51–57

    PubMed  CAS  Google Scholar 

  53. Prueitt RL, Ross JL, Zinn AR (2000) Physical mapping of nine Xq translocation breakpoints and identification of XPNPEP2 as a premature ovarian failure candidate gene. Cytogenet Cell Genet 89:44–50

    PubMed  CAS  Google Scholar 

  54. Wittenberger MD, Hagerman RJ, Sherman SL, McConkie-Rosell A, Welt CK, Rebar RW, Corrigan EC, Simpson JL, Nelson LM (2007) The FMR1 premutation and reproduction. Fertil Steril 87:456–465

    PubMed  CAS  Google Scholar 

  55. Schwartz CE, Dean J, Howard-Peebles PN, Bugge M, Mikkelsen M, Tommerup N, Hull C, Hagerman R, Holden JJ, Stevenson RE (1994) Obstetrical and gynecological complications in fragile X carriers: a multicenter study. Am J Med Genet 51:400–402

    PubMed  CAS  Google Scholar 

  56. Allingham-Hawkins DJ, Babul-Hirji R, Chitayat D, Holden JJ, Yang KT, Lee C, Hudson R, Gorwill H, Nolin SL, Glicksman A, Jenkins EC, Brown WT, Howard-Peebles PN, Becchi C, Cummings E, Fallon L, Seitz S, Black SH, Vianna-Morgante AM, Costa SS, Otto PA, Mingroni-Netto RC, Murray A, Webb J, Vieri F et al (1999) Fragile X premutation is a significant risk factor for premature ovarian failure: the International Collaborative POF in Fragile X study–preliminary data. Am J Med Genet 83:322–325

    PubMed Central  PubMed  CAS  Google Scholar 

  57. Sullivan AK, Marcus M, Epstein MP, Allen EG, Anido AE, Paquin JJ, Yadav-Shah M, Sherman SL (2005) Association of FMR1 repeat size with ovarian dysfunction. Hum Reprod 20:402–412

    PubMed  CAS  Google Scholar 

  58. Foresta C, Ferlin A, Gianaroli L, Dallapiccola B (2002) Guidelines for the appropriate use of genetic tests in infertile couples. Eur J Hum Genet 10:303–312

    PubMed  Google Scholar 

  59. Simpson JL, Christakos AC, Horwith M, Silverman FS (1971) Gonadal dysgenesis in individuals with apparently normal chromosomal complements: tabulation of cases and compilation of genetic data. Birth Defects Orig Artic Ser 7:215–228

    PubMed  CAS  Google Scholar 

  60. Simpson JL (1979) Gonadal dysgenesis and sex chromosome abnormalities. Phenotypic/karyotypic correlations. In: Vallet HL, Porter IH (eds) Genetic mechanisms of sexual development. Academic, New York, NY

    Google Scholar 

  61. Aittomaki K (1994) The genetics of XX gonadal dysgenesis. Am J Hum Genet 54:844–851

    PubMed Central  PubMed  CAS  Google Scholar 

  62. Aittomaki K, Lucena JL, Pakarinen P, Sistonen P, Tapanainen J, Gromoll J, Kaskikari R, Sankila EM, Lehvaslaiho H, Engel AR, Nieschlag E, Huhtaniemi I, de la Chapelle A (1995) Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell 82:959–968

    PubMed  CAS  Google Scholar 

  63. Simpson JL (1976) Disorders of sexual differentiation: etiology and clinical delineation. Monograph with chapters by J.E. Jirasek, N. G. Kase, and L. Speroff. Academic, New York, NY

    Google Scholar 

  64. Matthews CH, Borgato S, Beck-Peccoz P, Adams M, Tone Y, Gambino G, Casagrande S, Tedeschini G, Benedetti A, Chatterjee VK (1993) Primary amenorrhoea and infertility due to a mutation in the beta-subunit of follicle-stimulating hormone. Nat Genet 5:83–86

    PubMed  CAS  Google Scholar 

  65. Layman LC, Amde S, Cohen DP, Jin M, Xie J (1998) The Finnish follicle-stimulating hormone receptor gene mutation is rare in North American women with 46,XX ovarian failure. Fertil Steril 69:300–302

    PubMed  CAS  Google Scholar 

  66. Liu JY, Gromoll J, Cedars MI, La Barbera AR (1998) Identification of allelic variants in the follicle-stimulating hormone receptor genes of females with or without hypergonadotropic amenorrhea. Fertil Steril 70:326–331

    PubMed  CAS  Google Scholar 

  67. Simoni M, Gromoll J, Nieschlag E (1997) The follicle-stimulating hormone receptor: biochemistry, molecular biology, physiology, and pathophysiology. Endocr Rev 18:739–773

    PubMed  CAS  Google Scholar 

  68. da Fonte Kohek MB, Batista MC, Russell AJ, Vass K, Giacaglia LR, Mendonca BB, Latronico AC (1998) No evidence of the inactivating mutation (C566T) in the follicle-stimulating hormone receptor gene in Brazilian women with premature ovarian failure. Fertil Steril 70:565–567

    PubMed  Google Scholar 

  69. de la Chesnaye E, Canto P, Ulloa-Aguirre A, Mendez JP (2001) No evidence of mutations in the follicle-stimulating hormone receptor gene in Mexican women with 46, XX pure gonadal dysgenesis. Am J Med Genet 98:125–128

    PubMed  Google Scholar 

  70. Touraine P, Beau I, Gougeon A, Meduri G, Desroches A, Pichard C, Detoeuf M, Paniel B, Prieur M, Zorn JR, Milgrom E, Kuttenn F, Misrahi M (1999) New natural inactivating mutations of the follicle-stimulating hormone receptor: correlations between receptor function and phenotype. Mol Endocrinol 13:1844–1854

    PubMed  CAS  Google Scholar 

  71. Sultan C, Lumbroso S (1998) LH receptor defects. In: Kempers RD, Cohen J, Haney AF, Younger JB (eds) Fertility and reproductive medicine - Proceedings of the XVI World congress on fertility and sterility. Elsevier Science, San Francisco, CA

    Google Scholar 

  72. Latronico AC, Chai Y, Arnhold IJ, Liu X, Mendonca BB, Segaloff DL (1998) A homozygous microdeletion in helix 7 of the luteinizing hormone receptor associated with familial testicular and ovarian resistance is due to both decreased cell surface expression and impaired effector activation by the cell surface receptor. Mol Endocrinol 12:442–450

    PubMed  CAS  Google Scholar 

  73. Matzuk MM, Lamb DJ (2002) Genetic dissection of mammalian fertility pathways. Nat Cell Biol 4(Suppl):s41–49

    PubMed  Google Scholar 

  74. Yanase T, Kagimoto M, Suzuki S, Hashiba K, Simpson ER, Waterman MR (1989) Deletion of a phenylalanine in the N-terminal region of human cytochrome P-450(17 alpha) results in partial combined 17 alpha-hydroxylase/17,20-lyase deficiency. J Biol Chem 264:18076–18082

    PubMed  CAS  Google Scholar 

  75. Woad KJ, Pearson SM, Harris SE, Gersak K, Shelling AN (2009) Investigating the association between inhibin alpha gene promoter polymorphisms and premature ovarian failure. Fertil Steril 91:62–66

    PubMed  CAS  Google Scholar 

  76. Shelling AN, Burton KA, Chand AL, van Ee CC, France JT, Farquhar CM, Milsom SR, Love DR, Gersak K, Aittomaki K, Winship IM (2000) Inhibin: a candidate gene for premature ovarian failure. Hum Reprod 15:2644–2649

    PubMed  CAS  Google Scholar 

  77. Marozzi A, Porta C, Vegetti W, Crosignani PG, Tibiletti MG, Dalpra L, Ginelli E (2002) Mutation analysis of the inhibin alpha gene in a cohort of Italian women affected by ovarian failure. Hum Reprod 17:1741–1745

    PubMed  CAS  Google Scholar 

  78. Dixit H, Deendayal M, Singh L (2004) Mutational analysis of the mature peptide region of inhibin genes in Indian women with ovarian failure. Hum Reprod 19:1760–1764

    PubMed  CAS  Google Scholar 

  79. Prakash GJ, Ravi Kanth VV, Shelling AN, Rozati R, Sujatha M (2010) Mutational analysis of inhibin alpha gene revealed three novel variations in Indian women with premature ovarian failure. Fertil Steril 94:90–98

    PubMed  CAS  Google Scholar 

  80. Shelling AN (2010) Premature ovarian failure. Reproduction 140:633–641

    PubMed  CAS  Google Scholar 

  81. Chand AL, Ooi GT, Harrison CA, Shelling AN, Robertson DM (2007) Functional analysis of the human inhibin alpha subunit variant A257T and its potential role in premature ovarian failure. Hum Reprod 22:3241–3248

    PubMed  CAS  Google Scholar 

  82. Chand AL, Harrison CA, Shelling AN (2010) Inhibin and premature ovarian failure. Hum Reprod Update 16:39–50

    PubMed  CAS  Google Scholar 

  83. Dixit H, Rao LK, Padmalatha V, Kanakavalli M, Deenadayal M, Gupta N, Chakravarty B, Singh L (2005) Mutational screening of the coding region of growth differentiation factor 9 gene in Indian women with ovarian failure. Menopause 12:749–754

    PubMed  Google Scholar 

  84. Simsek E, Ozdemir I, Lin L, Achermann JC (2005) Isolated 17,20-lyase (desmolase) deficiency in a 46,XX female presenting with delayed puberty. Fertil Steril 83:1548–1551

    PubMed  Google Scholar 

  85. Araki S, Chikazawa K, Sekiguchi I, Yamauchi H, Motoyama M, Tamada T (1987) Arrest of follicular development in a patient with 17 alpha-hydroxylase deficiency: folliculogenesis in association with a lack of estrogen synthesis in the ovaries. Fertil Steril 47:169–172

    PubMed  CAS  Google Scholar 

  86. Rabinovici J, Blankstein J, Goldman B, Rudak E, Dor Y, Pariente C, Geier A, Lunenfeld B, Mashiach S (1989) In vitro fertilization and primary embryonic cleavage are possible in 17 alpha-hydroxylase deficiency despite extremely low intrafollicular 17 beta-estradiol. J Clin Endocrinol Metab 68:693–697

    PubMed  CAS  Google Scholar 

  87. Simpson ER (1998) Genetic mutations resulting in estrogen insufficiency in the male. Mol Cell Endocrinol 145:55–59

    PubMed  CAS  Google Scholar 

  88. Ito Y, Fisher CR, Conte FA, Grumbach MM, Simpson ER (1993) Molecular basis of aromatase deficiency in an adult female with sexual infantilism and polycystic ovaries. Proc Natl Acad Sci U S A 90:11673–11677

    PubMed Central  PubMed  CAS  Google Scholar 

  89. Conte FA, Grumbach MM, Ito Y, Fisher CR, Simpson ER (1994) A syndrome of female pseudohermaphrodism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase (P450arom). J Clin Endocrinol Metab 78:1287–1292

    PubMed  CAS  Google Scholar 

  90. Mullis PE, Yoshimura N, Kuhlmann B, Lippuner K, Jaeger P, Harada H (1997) Aromatase deficiency in a female who is compound heterozygote for two new point mutations in the P450arom gene: impact of estrogens on hypergonadotropic hypogonadism, multicystic ovaries, and bone densitometry in childhood. J Clin Endocrinol Metab 82:1739–1745

    PubMed  CAS  Google Scholar 

  91. Mansouri MR, Schuster J, Badhai J, Stattin EL, Losel R, Wehling M, Carlsson B, Hovatta O, Karlstrom PO, Golovleva I, Toniolo D, Bione S, Peluso J, Dahl N (2008) Alterations in the expression, structure and function of progesterone receptor membrane component-1 (PGRMC1) in premature ovarian failure. Hum Mol Genet 17:3776–3783

    PubMed Central  PubMed  CAS  Google Scholar 

  92. Crisponi L, Deiana M, Loi A, Chiappe F, Uda M, Amati P, Bisceglia L, Zelante L, Nagaraja R, Porcu S, Ristaldi MS, Marzella R, Rocchi M, Nicolino M, Lienhardt-Roussie A, Nivelon A, Verloes A, Schlessinger D, Gasparini P, Bonneau D, Cao A, Pilia G (2001) The putative forkhead transcription factor FOXL2 is mutated in blepharophimosis/ptosis/epicanthus inversus syndrome. Nat Genet 27:159–166

    PubMed  CAS  Google Scholar 

  93. Harris SE, Chand AL, Winship IM, Gersak K, Aittomaki K, Shelling AN (2002) Identification of novel mutations in FOXL2 associated with premature ovarian failure. Mol Hum Reprod 8:729–733

    PubMed  CAS  Google Scholar 

  94. Gersak K, Harris SE, Smale WJ, Shelling AN (2004) A novel 30 bp deletion in the FOXL2 gene in a phenotypically normal woman with primary amenorrhoea: case report. Hum Reprod 19:2767–2770

    PubMed  CAS  Google Scholar 

  95. De Baere E, Dixon MJ, Small KW, Jabs EW, Leroy BP, Devriendt K, Gillerot Y, Mortier G, Meire F, Van Maldergem L, Courtens W, Hjalgrim H, Huang S, Liebaers I, Van Regemorter N, Touraine P, Praphanphoj V, Verloes A, Udar N, Yellore V, Chalukya M, Yelchits S, De Paepe A, Kuttenn F, Fellous M, Veitia R, Messiaen L (2001) Spectrum of FOXL2 gene mutations in blepharophimosis-ptosis-epicanthus inversus (BPES) families demonstrates a genotype–phenotype correlation. Hum Mol Genet 10:1591–1600

    PubMed  Google Scholar 

  96. Qin Y, Choi Y, Zhao H, Simpson JL, Chen ZJ, Rajkovic A (2007) NOBOX homeobox mutation causes premature ovarian failure. Am J Hum Genet 81:576–581

    PubMed Central  PubMed  CAS  Google Scholar 

  97. Castrillon DH, Miao L, Kollipara R, Horner JW, DePinho RA (2003) Suppression of ovarian follicle activation in mice by the transcription factor Foxo3a. Science 301:215–218

    Google Scholar 

  98. Chand AL, Ponnampalam AP, Harris SE, Winship IM, Shelling AN (2006) Mutational analysis of BMP15 and GDF9 as candidate genes for premature ovarian failure. Fertil Steril 86:1009–1012

    PubMed  CAS  Google Scholar 

  99. Wang B, Wen Q, Ni F, Zhou S, Wang J, Cao Y, Ma X (2010) Analyses of growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15) mutation in Chinese women with premature ovarian failure. Clin Endocrinol 72:135–136

    CAS  Google Scholar 

  100. Demirhan O, Turkmen S, Schwabe GC, Soyupak S, Akgul E, Tastemir D, Karahan D, Mundlos S, Lehmann K (2005) A homozygous BMPR1B mutation causes a new subtype of acromesomelic chondrodysplasia with genital anomalies. J Med Genet 42:314–317

    PubMed Central  PubMed  CAS  Google Scholar 

  101. Yi SE, LaPolt PS, Yoon BS, Chen JY, Lu JK, Lyons KM (2001) The type I BMP receptor BmprIB is essential for female reproductive function. Proc Natl Acad Sci U S A 98:7994–7999

    PubMed Central  PubMed  CAS  Google Scholar 

  102. Wilson T, Wu XY, Juengel JL, Ross IK, Lumsden JM, Lord EA, Dodds KG, Walling GA, McEwan JC, O’Connell AR, McNatty KP, Montgomery GW (2001) Highly prolific Booroola sheep have a mutation in the intracellular kinase domain of bone morphogenetic protein IB receptor (ALK-6) that is expressed in both oocytes and granulosa cells. Biol Reprod 64:1225–1235

    PubMed  CAS  Google Scholar 

  103. Zhao H, Chen ZJ, Qin Y, Shi Y, Wang S, Choi Y, Simpson JL, Rajkovic A (2008) Transcription factor FIGLA is mutated in patients with premature ovarian failure. Am J Hum Genet 82:1342–1348

    PubMed Central  PubMed  CAS  Google Scholar 

  104. Wang J, Wang B, Song J, Suo P, Ni F, Chen B, Ma X, Cao Y (2011) New candidate gene POU5F1 associated with premature ovarian failure in Chinese patients. Reprod Biomed Online 22:312–316

    PubMed  Google Scholar 

  105. Kang H, Lee SK, Kim MH, Song J, Bae SJ, Kim NK, Lee SH, Kwack K (2008) Parathyroid hormone-responsive B1 gene is associated with premature ovarian failure. Hum Reprod 23:1457–1465

    PubMed  CAS  Google Scholar 

  106. Kaufman FR, Kogut MD, Donnell GN, Goebelsmann U, March C, Koch R (1981) Hypergonadotropic hypogonadism in female patients with galactosemia. N Engl J Med 304:994–998

    PubMed  CAS  Google Scholar 

  107. Waggoner DD, Buist NR, Donnell GN (1990) Long-term prognosis in galactosaemia: results of a survey of 350 cases. J Inher Metab Dis 13:802–818

    PubMed  CAS  Google Scholar 

  108. Levy HL, Driscoll SG, Porensky RS, Wender DF (1984) Ovarian failure in galactosemia. N Engl J Med 310:50

    PubMed  CAS  Google Scholar 

  109. Leslie ND, Yager KL, McNamara PD, Segal S (1996) A mouse model of galactose-1-phosphate uridyl transferase deficiency. Biochem Mol Med 59:7–12

    PubMed  CAS  Google Scholar 

  110. Badik JR, Castaneda U, Gleason TJ, Spencer JB, Epstein MP, Ficicioglu C, Fitzgerald K, Fridovich-Keil JL (2011) Ovarian function in Duarte galactosemia. Fertil Steril 96(469–473):e461

    Google Scholar 

  111. Bjursell C, Stibler H, Wahlstrom J, Kristiansson B, Skovby F, Stromme P, Blennow G, Martinsson T (1997) Fine mapping of the gene for carbohydrate-deficient glycoprotein syndrome, type I (CDG1): linkage disequilibrium and founder effect in Scandinavian families. Genomics 39:247–253

    PubMed  CAS  Google Scholar 

  112. Matthijs G, Schollen E, Pardon E, Veiga-Da-Cunha M, Jaeken J, Cassiman JJ, Van Schaftingen E (1997) Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome). Nat Genet 16:88–92

    PubMed  CAS  Google Scholar 

  113. de Zegher F, Jaeken J (1995) Endocrinology of the carbohydrate-deficient glycoprotein syndrome type 1 from birth through adolescence. Pediatr Res 37:395–401

    PubMed  Google Scholar 

  114. Kristiansson B, Stibler H, Wide L (1995) Gonadal function and glycoprotein hormones in the carbohydrate-deficient glycoprotein (CDG) syndrome. Acta Paediatr 84:655–659

    PubMed  CAS  Google Scholar 

  115. Wang CY, Davoodi-Semiromi A, Huang W, Connor E, Shi JD, She JX (1998) Characterization of mutations in patients with autoimmune polyglandular syndrome type 1 (APS1). Hum Genet 103:681–685

    PubMed  CAS  Google Scholar 

  116. Boltshauser E, Barth PG, Troost D, Martin E, Stallmach T (2002) “Vanishing white matter” and ovarian dysgenesis in an infant with cerebro-oculo-facio-skeletal phenotype. Neuropediatrics 33:57–62

    PubMed  CAS  Google Scholar 

  117. Schiffmann R, Tedeschi G, Kinkel RP, Trapp BD, Frank JA, Kaneski CR, Brady RO, Barton NW, Nelson L, Yanovski JA (1997) Leukodystrophy in patients with ovarian dysgenesis. Ann Neurol 41:654–661

    PubMed  CAS  Google Scholar 

  118. Fogli A, Rodriguez D, Eymard-Pierre E, Bouhour F, Labauge P, Meaney BF, Zeesman S, Kaneski CR, Schiffmann R, Boespflug-Tanguy O (2003) Ovarian failure related to eukaryotic initiation factor 2B mutations. Am J Hum Genet 72:1544–1550

    PubMed Central  PubMed  CAS  Google Scholar 

  119. Fogli A, Gauthier-Barichard F, Schiffmann R, Vanderhoof VH, Bakalov VK, Nelson LM, Boespflug-Tanguy O (2004) Screening for known mutations in EIF2B genes in a large panel of patients with premature ovarian failure. BMC Womens Health 4:8

    PubMed Central  PubMed  Google Scholar 

  120. Skre H, Bassoe HH, Berg K, Frovig AG (1976) Cerebellar ataxia and hypergonadotropic hypogonadism in two kindreds. Chance concurrence, pleiotropism or linkage? Clin Genet 9:234–244

    PubMed  CAS  Google Scholar 

  121. De Michele G, Filla A, Striano S, Rimoldi M, Campanella G (1993) Heterogeneous findings in four cases of cerebellar ataxia associated with hypogonadism (Holmes’ type ataxia). Clin Neurol Neurosurg 95:23–28

    PubMed  Google Scholar 

  122. Linssen WH, Van den Bent MJ, Brunner HG, Poels PJ (1994) Deafness, sensory neuropathy, and ovarian dysgenesis: a new syndrome or a broader spectrum of Perrault syndrome? Am J Med Genet 51:81–82

    PubMed  CAS  Google Scholar 

  123. Amor DJ, Delatycki MB, Gardner RJ, Storey E (2001) New variant of familial cerebellar ataxia with hypergonadotropic hypogonadism and sensorineural deafness. Am J Med Genet 99:29–33

    PubMed  CAS  Google Scholar 

  124. Groppe J, Greenwald J, Wiater E, Rodriguez-Leon J, Economides AN, Kwiatkowski W, Affolter M, Vale WW, Belmonte JC, Choe S (2002) Structural basis of BMP signalling inhibition by the cystine knot protein Noggin. Nature 420:636–642

    PubMed  CAS  Google Scholar 

  125. Kosaki K, Sato S, Hasegawa T, Matsuo N, Suzuki T, Ogata T (2004) Premature ovarian failure in a female with proximal symphalangism and Noggin mutation. Fertil Steril 81:1137–1139

    PubMed  Google Scholar 

  126. Perrault M, Klotz P, Housset E (1951) Deux cas de syndrome de Turner avec surdi-mutite dans une meme fratrie. Bull Mem Soc Med Hop Paris 67:79–84

    PubMed  CAS  Google Scholar 

  127. Josso N, de Grouchy J, Frezal J, Lamy M (1963) Le syndrome de Turner familial etude de deux families avec caryotypes XO er XX. Ann Pediatr 10:163–167

    CAS  Google Scholar 

  128. Nishi Y, Hamamoto K, Kajiyama M, Kawamura I (1988) The Perrault syndrome: clinical report and review. Am J Med Genet 31:623–629

    PubMed  CAS  Google Scholar 

  129. Pallister PD, Opitz JM (1979) The Perrault syndrome: autosomal recessive ovarian dysgenesis with facultative, non-sex-limited sensorineural deafness. Am J Med Genet 4:239–246

    PubMed  CAS  Google Scholar 

  130. Simon AM, Goodenough DA, Li E, Paul DL (1997) Female infertility in mice lacking connexin 37. Nature 385:525–529

    PubMed  CAS  Google Scholar 

  131. Watkins WJ, Umbers AJ, Woad KJ, Harris SE, Winship IM, Gersak K, Shelling AN (2006) Mutational screening of FOXO3A and FOXO1A in women with premature ovarian failure. Fertil Steril 86:1518–1521

    PubMed  CAS  Google Scholar 

  132. Wang B, Mu Y, Ni F, Zhou S, Wang J, Cao Y, Ma X (2010) Analysis of FOXO3 mutation in 114 Chinese women with premature ovarian failure. Reprod Biomed Online 20:499–503

    PubMed  Google Scholar 

  133. Pangas SA, Choi Y, Ballow DJ, Zhao Y, Westphal H, Matzuk MM, Rajkovic A (2006) Oogenesis requires germ cell-specific transcriptional regulators Sohlh1 and Lhx8. Proc Natl Acad Sci U S A 103:8090–8095

    PubMed Central  PubMed  CAS  Google Scholar 

  134. Qin Y, Zhao H, Kovanci E, Simpson JL, Chen ZJ, Rajkovic A (2008) Analysis of LHX8 mutation in premature ovarian failure. Fertil Steril 89:1012–1014

    PubMed Central  PubMed  Google Scholar 

  135. Tsuda M, Sasaoka Y, Kiso M, Abe K, Haraguchi S, Kobayashi S, Saga Y (2003) Conserved role of nanos proteins in germ cell development. Science 301:1239–1241

    PubMed  CAS  Google Scholar 

  136. Qin Y, Zhao H, Kovanci E, Simpson JL, Chen ZJ, Rajkovic A (2007) Mutation analysis of NANOS3 in 80 Chinese and 88 Caucasian women with premature ovarian failure. Fertil Steril 88:1465–1467

    PubMed Central  PubMed  Google Scholar 

  137. Mehlmann LM, Saeki Y, Tanaka S, Brennan TJ, Evsikov AV, Pendola FL, Knowles BB, Eppig JJ, Jaffe LA (2004) The Gs-linked receptor GPR3 maintains meiotic arrest in mammalian oocytes. Science 306:1947–1950

    PubMed  CAS  Google Scholar 

  138. Kovanci E, Simpson JL, Amato P, Rohozinski J, Heard MJ, Bishop CE, Carson SA (2008) Oocyte-specific G-protein-coupled receptor 3 (GPR3): no perturbations found in 82 women with premature ovarian failure (first report). Fertil Steril 90:1269–1271

    PubMed  CAS  Google Scholar 

  139. Zhou S, Wang B, Ni F, Wang J, Cao Y, Ma X (2010) GPR3 may not be a potential candidate gene for premature ovarian failure. Reprod Biomed Online 20:53–55

    PubMed  CAS  Google Scholar 

  140. Richards KA, Fukai K, Oiso N, Paller AS (2001) A novel KIT mutation results in piebaldism with progressive depigmentation. J Am Acad Dermatol 44:288–292

    PubMed  CAS  Google Scholar 

  141. Shibanuma K, Tong ZB, Vanderhoof VH, Vanevski K, Nelson LM (2002) Investigation of KIT gene mutations in women with 46,XX spontaneous premature ovarian failure. BMC Womens Health 2:8

    PubMed Central  PubMed  Google Scholar 

  142. Suzumori N, Burns KH, Yan W, Matzuk MM (2003) RFPL4 interacts with oocyte proteins of the ubiquitin-proteasome degradation pathway. Proc Natl Acad Sci U S A 100:550–555

    PubMed Central  PubMed  CAS  Google Scholar 

  143. Suzumori N, Pangas SA, Rajkovic A (2007) Candidate genes for premature ovarian failure. Curr Med Chem 14:353–357

    PubMed  CAS  Google Scholar 

  144. Mandon-Pepin B, Touraine P, Kuttenn F, Derbois C, Rouxel A, Matsuda F, Nicolas A, Cotinot C, Fellous M (2008) Genetic investigation of four meiotic genes in women with premature ovarian failure. Eur J Endocrinol 158:107–115

    PubMed  CAS  Google Scholar 

  145. Shimizu Y, Kimura F, Takebayashi K, Fujiwara M, Takakura K, Takahashi K (2009) Mutational analysis of the PTEN gene in women with premature ovarian failure. Acta Obstet Gynecol Scand 88:824–825

    PubMed  CAS  Google Scholar 

  146. Ojeda D, Lakhal B, Fonseca DJ, Braham R, Landolsi H, Mateus HE, Restrepo CM, Elghezal H, Saad A, Laissue P (2011) Sequence analysis of the CDKN1B gene in patients with premature ovarian failure reveals a novel mutation potentially related to the phenotype. Fertil Steril 95(2658–2660):e2651

    Google Scholar 

  147. Wang B, Ni F, Li L, Wei Z, Zhu X, Wang J, Cao Y, Ma X (2010) Analysis of cyclin-dependent kinase inhibitor 1B mutation in Han Chinese women with premature ovarian failure. Reprod Biomed Online 21:212–214

    PubMed  CAS  Google Scholar 

  148. Durlinger AL, Kramer P, Karels B, de Jong FH, Uilenbroek JT, Grootegoed JA, Themmen AP (1999) Control of primordial follicle recruitment by anti-Mullerian hormone in the mouse ovary. Endocrinology 140:5789–5796

    PubMed  CAS  Google Scholar 

  149. Wang HQ, Takakura K, Takebayashi K, Noda Y (2002) Mutational analysis of the mullerian-inhibiting substance gene and its receptor gene in Japanese women with polycystic ovary syndrome and premature ovarian failure. Fertil Steril 78:1329–1330

    PubMed  Google Scholar 

  150. Luoma P, Melberg A, Rinne JO, Kaukonen JA, Nupponen NN, Chalmers RM, Oldfors A, Rautakorpi I, Peltonen L, Majamaa K, Somer H, Suomalainen A (2004) Parkinsonism, premature menopause, and mitochondrial DNA polymerase gamma mutations: clinical and molecular genetic study. Lancet 364:875–882

    PubMed  CAS  Google Scholar 

  151. Pagnamenta AT, Taanman JW, Wilson CJ, Anderson NE, Marotta R, Duncan AJ, Bitner-Glindzicz M, Taylor RW, Laskowski A, Thorburn DR, Rahman S (2006) Dominant inheritance of premature ovarian failure associated with mutant mitochondrial DNA polymerase gamma. Hum Reprod 21:2467–2473

    PubMed  CAS  Google Scholar 

  152. Granat M, Amar A, Mor-Yosef S, Brautbar C, Schenker JG (1983) Familial gonadal germinative failure: endocrine and human leukocyte antigen studies. Fertil Steril 40:215–219

    PubMed  CAS  Google Scholar 

  153. Smith A, Fraser IS, Noel M (1979) Three siblings with premature gonadal failure. Fertil Steril 32:528–530

    PubMed  CAS  Google Scholar 

  154. Al-Awadi SA, Farag TI, Teebi AS, Naguib K, el-Khalifa MY, Kelani Y, Al-Ansari A, Schimke RN (1985) Primary hypogonadism and partial alopecia in three sibs with mullerian hypoplasia in the affected females. Am J Med Genet 22:619–622

    PubMed  CAS  Google Scholar 

  155. Mikati MA, Najjar SS, Sahli IF, Melhem RE, Mansour S, Der Kaloustian VM (1985) Microcephaly, hypergonadotropic hypogonadism, short stature, and minor anomalies: a new syndrome. Am J Med Genet 22:599–608

    PubMed  CAS  Google Scholar 

  156. Simpson JL (1999) Genetics of the female reproductive ducts. Am J Med Genet 89:224–239

    PubMed  CAS  Google Scholar 

  157. Elias S, Simpson JL, Carson SA, Malinak LR, Buttram VC Jr (1984) Genetics studies in incomplete mullerian fusion. Obstet Gynecol 63:276–279

    PubMed  CAS  Google Scholar 

  158. Ergun A, Pabuccu R, Atay V, Kucuk T, Duru NK, Gungor S (1997) Three sisters with septate uteri: another reference to bidirectional theory. Hum Reprod 12:140–142

    PubMed  CAS  Google Scholar 

  159. Hay D (1961) Uterus unicollis and its relationship to pregnancy. J Obstet Gynaecol Br Emp 68:361–377

    PubMed  CAS  Google Scholar 

  160. Holmes JA (1956) Congenital abnormalities of the uterus and pregnancy. Br Med J 1:1144–1147

    PubMed Central  PubMed  CAS  Google Scholar 

  161. Nykiforuk NE (1938) Uterus Didelphys. Can Med Assoc J 38:175

    PubMed Central  PubMed  CAS  Google Scholar 

  162. Polishuk WZ, Ron MA (1974) Familial bicornuate and double uterus. Am J Obstet Gynecol 119:982–987

    PubMed  CAS  Google Scholar 

  163. Stevenson AC, Dudgeon MY, Mc CH (1959) Observations on the results of pregnancies in women resident in Belfast. II. Abortions, hydatidiform moles and ectopic pregnancies. Ann Hum Genet 23:395–414

    PubMed  CAS  Google Scholar 

  164. Tyler GT (1939) Didelphys, in sisters. Am J Surg 45:337–338

    Google Scholar 

  165. Verp MS, Simpson JL, Elias S, Carson SA, Sarto GE, Feingold M (1983) Heritable aspects of uterine anomalies. I. Three familial aggregates with Mullerian fusion anomalies. Fertil Steril 40:80–85

    PubMed  CAS  Google Scholar 

  166. Way S (1945) The influence of minor degrees of failure of fusion of the Mullerian ducts on pregnancy and labor. J Obstet Gynaecol Br Emp 52:325–333

    Google Scholar 

  167. Ma J, Qin Y, Liu W, Duan H, Xia M, Chen ZJ (2011) Analysis of PBX1 mutations in 192 Chinese women with Mullerian duct abnormalities. Fertil Steril 95:2615–2617

    PubMed  CAS  Google Scholar 

  168. Schnabel CA, Selleri L, Cleary ML (2003) Pbx1 is essential for adrenal development and urogenital differentiation. Genesis 37:123–130

    PubMed  CAS  Google Scholar 

  169. Donnenfeld AE, Schrager DS, Corson SL (1992) Update on a family with hand-foot-genital syndrome: hypospadias and urinary tract abnormalities in two boys from the fourth generation. Am J Med Genet 44:482–484

    PubMed  CAS  Google Scholar 

  170. Stern AM, Gall JC Jr, Perry BL, Stimson CW, Weitkamp LR, Poznanski AK (1970) The hand-food-uterus syndrome: a new hereditary disorder characterized by hand and foot dysplasia, dermatoglyphic abnormalities, and partial duplication of the female genital tract. J Pediatr 77:109–116

    PubMed  CAS  Google Scholar 

  171. Mortlock DP, Innis JW (1997) Mutation of HOXA13 in hand-foot-genital syndrome. Nat Genet 15:179–180

    PubMed  CAS  Google Scholar 

  172. Goodman FR, Bacchelli C, Brady AF, Brueton LA, Fryns JP, Mortlock DP, Innis JW, Holmes LB, Donnenfeld AE, Feingold M, Beemer FA, Hennekam RC, Scambler PJ (2000) Novel HOXA13 mutations and the phenotypic spectrum of hand-foot-genital syndrome. Am J Hum Genet 67:197–202

    PubMed Central  PubMed  CAS  Google Scholar 

  173. Hennekam RC (1989) Acral-genital anomalies combined with ear anomalies. Am J Med Genet 34:454–455

    PubMed  CAS  Google Scholar 

  174. Utsch B, Becker K, Brock D, Lentze MJ, Bidlingmaier F, Ludwig M (2002) A novel stable polyalanine [poly(A)] expansion in the HOXA13 gene associated with hand-foot-genital syndrome: proper function of poly(A)-harbouring transcription factors depends on a critical repeat length? Hum Genet 110:488–494

    PubMed  CAS  Google Scholar 

  175. Jones HW Jr, Rock JA (1983) Reparative and constructive surgery of the female genital tract. Williams & Wilkins, Baltimore

    Google Scholar 

  176. Lodi A (1951) Contributo clinco statistico sulle Malformazioni della vagina osservate nella Clinical Obstetrica e Gineocologica di Milano del 1906 al 1950. Ann Ostet Ginecol 73:1246–1285

    PubMed  CAS  Google Scholar 

  177. McKusick VA (1978) The William Allan Memorial Award Lecture: Genetic nosology: three approaches. Am J Hum Genet 30:105–122

    PubMed Central  PubMed  CAS  Google Scholar 

  178. McKusick VA, Bauer RL, Koop CE, Scott RB (1964) Hydrometrocolpos as a Simply Inherited Malformation. JAMA 189:813–816

    PubMed  CAS  Google Scholar 

  179. Kaufman RL, McAlister WH, Ho CK, Hartmann AF (1974) Family studies in congenital heart disease VI. The association of severe obstructive left heart lesions, vertebral and renal anomalies; a second family. Birth Defects Orig Artic Ser 10:93–104

    PubMed  CAS  Google Scholar 

  180. Chitayat D, Hahm SY, Marion RW, Sachs GS, Goldman D, Hutcheon RG, Weiss R, Cho S, Nitowsky HM (1987) Further delineation of the McKusick-Kaufman hydrometrocolpos-polydactyly syndrome. Am J Dis Child 141:1133–1136

    PubMed  CAS  Google Scholar 

  181. Stone DL, Slavotinek A, Bouffard GG, Banerjee-Basu S, Baxevanis AD, Barr M, Biesecker LG (2000) Mutation of a gene encoding a putative chaperonin causes McKusick-Kaufman syndrome. Nat Genet 25:79–82

    PubMed  CAS  Google Scholar 

  182. Winter JS, Kohn G, Mellman WJ, Wagner S (1968) A familial syndrome of renal, genital, and middle ear anomalies. J Pediatr 72:88–93

    PubMed  CAS  Google Scholar 

  183. King LA, Sanchez-Ramos L, Talledo OE, Reindollar RH (1987) Syndrome of genital, renal, and middle ear anomalies: a third family and report of a pregnancy. Obstet Gynecol 69:491–493

    PubMed  CAS  Google Scholar 

  184. Griffin JE, Edwards C, Madden JD, Harrod MJ, Wilson JD (1976) Congenital absence of the vagina. The Mayer-Rokitansky-Kuster-Hauser syndrome. Ann Intern Med 85:224–236

    PubMed  CAS  Google Scholar 

  185. Jones HW Jr, Mermut S (1972) Familial occurrence of congenital absence of the vagina. Am J Obstet Gynecol 114:1100–1101

    PubMed  Google Scholar 

  186. Kupperman JH (1963) Human endocrinology, vol 1. FA Davis, Philadelphia, PA

    Google Scholar 

  187. Lischke JH, Curtis CH, Lamb EJ (1973) Discordance of vaginal agenesis in monozygotic twins. Obstet Gynecol 41:920–924

    PubMed  CAS  Google Scholar 

  188. Carson SA, Simpson JL, Malinak LR, Elias S, Gerbie AB, Buttram VC Jr, Sarto GE (1983) Heritable aspects of uterine anomalies. II. Genetic analysis of Mullerian aplasia. Fertil Steril 40:86–90

    PubMed  CAS  Google Scholar 

  189. van Lingen BL, Reindollar RH, Davis AJ, Gray MR (1998) Further evidence that the WT1 gene does not have a role in the development of the derivatives of the mullerian duct. Am J Obstet Gynecol 179:597–603

    PubMed  Google Scholar 

  190. Petrozza JC, Gray MR, Davis AJ, Reindollar RH (1997) Congenital absence of the uterus and vagina is not commonly transmitted as a dominant genetic trait: outcomes of surrogate pregnancies. Fertil Steril 67:387–389

    PubMed  CAS  Google Scholar 

  191. Van Lingen BL, Eccles MR, Reindollar RH, al E. (1998) Molecular genetic analysis of the PAX2 gene in patients with gengenital absence of the uterus and vagina., Fertil Steril.

    Google Scholar 

  192. Zenteno JC, Carranza-Lira S, Kofman-Alfaro S (2004) Molecular analysis of the anti-Mullerian hormone, the anti-Mullerian hormone receptor, and galactose-1-phosphate uridyl transferase genes in patients with the Mayer-Rokitansky-Kuster-Hauser syndrome. Arch Gynecol Obstet 269:270–273

    PubMed  CAS  Google Scholar 

  193. Bhagavath B, Stelling JR, Van Lingen BL et al (1998) Congenital absence of the uterus and vagina (CAUV) is not associated with the N314D allele of the galactose-1-phosphate uridyl transferase (GALT) gene. J Soc Gynecol Investig 5:140

    Google Scholar 

  194. Cheroki C, Krepischi-Santos AC, Rosenberg C, Jehee FS, Mingroni-Netto RC, Pavanello Filho I, Zanforlin Filho S, Kim CA, Bagnoli VR, Mendonca BB, Szuhai K, Otto PA (2006) Report of a del22q11 in a patient with Mayer-Rokitansky-Kuster-Hauser (MRKH) anomaly and exclusion of WNT-4, RAR-gamma, and RXR-alpha as major genes determining MRKH anomaly in a study of 25 affected women. Am J Med Genet A 140:1339–1342

    PubMed  Google Scholar 

  195. Burel A, Mouchel T, Odent S, Tiker F, Knebelmann B, Pellerin I, Guerrier D (2006) Role of HOXA7 to HOXA13 and PBX1 genes in various forms of MRKH syndrome (congenital absence of uterus and vagina). J Negat Results Biomed 5:4

    PubMed Central  PubMed  Google Scholar 

  196. Philibert P, Biason-Lauber A, Rouzier R, Pienkowski C, Paris F, Konrad D, Schoenle E, Sultan C (2008) Identification and functional analysis of a new WNT4 gene mutation among 28 adolescent girls with primary amenorrhea and mullerian duct abnormalities: a French collaborative study. J Clin Endocrinol Metab 93:895–900

    PubMed  CAS  Google Scholar 

  197. Ravel C, Lorenco D, Dessolle L, Mandelbaum J, McElreavey K, Darai E, Siffroi JP (2009) Mutational analysis of the WNT gene family in women with Mayer-Rokitansky-Kuster-Hauser syndrome. Fertil Steril 91:1604–1607

    PubMed  CAS  Google Scholar 

  198. Drash A, Sherman F, Hartmann WH, Blizzard RM (1970) A syndrome of pseudohermaphroditism, Wilms’ tumor, hypertension, and degenerative renal disease. J Pediatr 76:585–593

    PubMed  CAS  Google Scholar 

  199. Clement-Ziza M, Khen N, Gonzales J, Cretolle-Vastel C, Picard JY, Tullio-Pelet A, Besmond C, Munnich A, Lyonnet S, Nihoul-Fekete C (2005) Exclusion of WNT4 as a major gene in Rokitansky-Kuster-Hauser anomaly. Am J Med Genet A 137:98–99

    PubMed  Google Scholar 

  200. Sandbacka M, Bruce S, Halttunen M, Puhakka M, Lahermo P, Hannula-Jouppi K, Lipsanen-Nyman M, Kere J, Aittomaki K, Laivuori H (2011) Methylation of H19 and its imprinted control region (H19 ICR1) in Mullerian aplasia. Fertil Steril 95:2703–2706

    PubMed  CAS  Google Scholar 

  201. Bendavid C, Pasquier L, Watrin T, Morcel K, Lucas J, Gicquel I, Dubourg C, Henry C, David V, Odent S, Leveque J, Pellerin I, Guerrier D (2007) Phenotypic variability of a 4q34→qter inherited deletion: MRKH syndrome in the daughter, cardiac defect and Fallopian tube cancer in the mother. Eur J Med Genet 50:66–72

    PubMed  Google Scholar 

  202. Bernardini L, Gimelli S, Gervasini C, Carella M, Baban A, Frontino G, Barbano G, Divizia MT, Fedele L, Novelli A, Bena F, Lalatta F, Miozzo M, Dallapiccola B (2009) Recurrent microdeletion at 17q12 as a cause of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome: two case reports. Orphanet J Rare Dis 4:25

    PubMed Central  PubMed  Google Scholar 

  203. Cheroki C, Krepischi-Santos AC, Szuhai K, Brenner V, Kim CA, Otto PA, Rosenberg C (2008) Genomic imbalances associated with mullerian aplasia. J Med Genet 45:228–232

    PubMed  CAS  Google Scholar 

  204. Ledig S, Schippert C, Strick R, Beckmann MW, Oppelt PG, Wieacker P (2011) Recurrent aberrations identified by array-CGH in patients with Mayer-Rokitansky-Kuster-Hauser syndrome. Fertil Steril 95:1589–1594

    PubMed  CAS  Google Scholar 

  205. Nik-Zainal S, Strick R, Storer M, Huang N, Rad R, Willatt L, Fitzgerald T, Martin V, Sandford R, Carter NP, Janecke AR, Renner SP, Oppelt PG, Oppelt P, Schulze C, Brucker S, Hurles M, Beckmann MW, Strissel PL, Shaw-Smith C (2011) High incidence of recurrent copy number variants in patients with isolated and syndromic Mullerian aplasia. J Med Genet 48:197–204

    PubMed Central  PubMed  Google Scholar 

  206. Sundaram UT, McDonald-McGinn DM, Huff D, Emanuel BS, Zackai EH, Driscoll DA, Bodurtha J (2007) Primary amenorrhea and absent uterus in the 22q11.2 deletion syndrome. Am J Med Genet A 143A:2016–2018

    PubMed Central  PubMed  CAS  Google Scholar 

  207. Gervasini C, Grati FR, Lalatta F, Tabano S, Gentilin B, Colapietro P, De Toffol S, Frontino G, Motta F, Maitz S, Bernardini L, Dallapiccola B, Fedele L, Larizza L, Miozzo M (2010) SHOX duplications found in some cases with type I Mayer-Rokitansky-Kuster-Hauser syndrome. Genet Med 12:634–640

    PubMed  Google Scholar 

  208. Sandbacka M, Halttunen M, Jokimaa V, Aittomaki K, Laivuori H (2011) Evaluation of SHOX copy number variations in patients with Mullerian aplasia. Orphanet J Rare Dis 6:53

    PubMed Central  PubMed  Google Scholar 

  209. Biason-Lauber A, Konrad D, Navratil F, Schoenle EJ (2004) A WNT4 mutation associated with Mullerian-duct regression and virilization in a 46,XX woman. N Engl J Med 351:792–798

    PubMed  CAS  Google Scholar 

  210. Vainio S, Heikkila M, Kispert A, Chin N, McMahon AP (1999) Female development in mammals is regulated by Wnt-4 signalling. Nature 397:405–409

    PubMed  CAS  Google Scholar 

  211. Duncan PA, Shapiro LR, Stangel JJ, Klein RM, Addonizio JC (1979) The MURCS association: Mullerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia. J Pediatr 95:399–402

    PubMed  CAS  Google Scholar 

  212. Wulfsberg EA, Grigbsy TM (1990) Rokitansky sequence in association with the facio-auriculo-vertebral sequence: part of a mesodermal malformation spectrum? Am J Med Genet 37:100–102

    PubMed  CAS  Google Scholar 

  213. Farag TI, Al-Awadi SA, Marafie MJ, Bastaki L, Al-Othman SA, Mohammed FM, Al Suliman IS, Murthy DS (1993) The newly recognised limb/pelvis-hypoplasia/aplasia syndrome: report of a Bedouin patient and review. J Med Genet 30:62–64

    PubMed Central  PubMed  CAS  Google Scholar 

  214. Teebi AS (1993) Limb/pelvis/uterus-hypoplasia/aplasia syndrome. J Med Genet 30:797

    PubMed Central  PubMed  CAS  Google Scholar 

  215. Hoffmann W, Grospietsch G, Kuhn W (1976) Thalidomide and female genital malformations. Lancet 2:794

    PubMed  CAS  Google Scholar 

  216. Griesinger G, Dafopoulos K, Schultze-Mosgau A, Schroder A, Felberbaum R, Diedrich K (2005) Mayer-Rokitansky-Kuster-Hauser syndrome associated with thrombocytopenia-absent radius syndrome. Fertil Steril 83:452–454

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Human and Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, AHC2 693, Miami, FL, 33199, USA

    Joe Leigh Simpson M.D.

  2. Department of Obstetrics and Gynecology, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, AHC2 693, Miami, FL, 33199, USA

    Joe Leigh Simpson M.D.

Authors
  1. Joe Leigh Simpson M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joe Leigh Simpson M.D. .

Editor information

Editors and Affiliations

  1. The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Cornell Medical College, New York, New York, USA

    Zev Rosenwaks

  2. Dept. Developmental & Regenerative Biology, Ichan School of Medicine at Mount Sinai, New York, New York, USA

    Paul M. Wassarman

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this protocol

Cite this protocol

Simpson, J.L. (2014). Genetics of Female Infertility Due to Anomalies of the Ovary and Mullerian Ducts. In: Rosenwaks, Z., Wassarman, P. (eds) Human Fertility. Methods in Molecular Biology, vol 1154. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0659-8_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-0659-8_3

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-0658-1

  • Online ISBN: 978-1-4939-0659-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation