Human Genetics

, Volume 96, Issue 1, pp 119–129 | Cite as

Isodicentric Y chromosome: cytogenetic, molecular and clinical studies and review of the literature

  • Cathy M. Tuck-Muller
  • Harold Chen
  • José E. Martínez
  • Chuen-Cheh Shen
  • Shibo Li
  • Christine Kusyk
  • Denise A. S. Batista
  • Yogendra M. Bhatnagar
  • Edmund Dowling
  • Wladimir Wertelecki
Case Report


Dicentrics are among the most common structural abnormalities of the human Y chromosome. Predicting the phenotypic consequences of different duplications and deletions of dicentric Y chromosomes is usually complicated by varying degrees of mosaicism (45,X cell lines), which may, in some cases, remain undetected. Molecular studies in patients with dicentric Y chromosomes have been few, and only two studies have attempted to determine the presence of SRY (the putative testis-determining factor gene). We report an 18-year-old female with short stature, amenorrhea, hirsutism, hypoplastic labia minora, and clitoromegaly who has a 45,X/46,X,idic(Y)(p11.32)/47,X,idic(Y)(p11.32),idic(Y) (p11.32) karyotype. Southern analysis using Y-specific probes (Y97, 2D6, 1F5, pY3.4) and polymerase chain reaction (PCR) analysis using primers for ZFY and SRY were positive for all loci tested, indicating that almost all of the Y chromosome was present. Our findings and an extensive review of the literature emphasize the importance of molecular analyses of abnormal Y chromosomes before any general conclusions can be reached concerning the relative effects of the Y-chromosome abnormality and mosaicism on sexual differentiation.


Polymerase Chain Reaction Internal Medicine Clinical Study Metabolic Disease Molecular Analysis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alexander DS, Soudek D, Laraya P (1978) Unstable dicentric iso(Yq) chromosome in a pseudohermaphrodite. Am J Med Genet 1:265–269Google Scholar
  2. Almedia JCC de, Llerena JC Jr, Jung M, Martins RR, Gomes DM, Reis DF, Cunha AG (1986) Combined cytogenetic techniques and non-fluorescent Y: cytologic evidences of dic(Yp)(q11) in a previously interpreted 46,X,Yq-. Ann Genet 29:114–118Google Scholar
  3. Armendares S. Buentello L, Salmanca F, Cantu-Garza J-M (1972) A dicentric Y chromosome without evidence of sex chromosomal mosaicism, 46,XYqdic, in a patient with features of Turner's syndrome. J Med Genet 9:96–131Google Scholar
  4. Armandares S, Salamanca F, Cos J, Chavarria C (1977) 45,X/46,X,dic(Yq) mosaicism and mixed gonadal dysgenesis: case report and review of the literature. Ann Genet 20:269–272Google Scholar
  5. Ataya KM, Dudin G, Mroueh A (1983) Dicentric i(Yq) chromosome and azoospermia. Am J Med Genet 14:583–590Google Scholar
  6. Batstone PJ, Faed MJW, Jung RT, Gosden J (1991) 45,X/46,X dic(Y) mosaicism in a phenotypic male. Arch Dis Child 66:252–253Google Scholar
  7. Bernstein R, Steinhaus KA, Cain MJ (1992) Prenatal application of fluorescent in situ hybridization (FISH) for identification of a mosaic Y-chromosome marker, idic(Yp). Prenat Diagn 12:709–716Google Scholar
  8. Berta P, Hawkins JR, Sinclair AH, Taylor A, Griffiths BL, Goodfellow PN, Fellous M (1990) Genetic evidence equating SRY and the testis-determining factor. Nature 348:448–454Google Scholar
  9. Blackman JA, Selzer SC, Patil S, Van Dyke DC (1991) Autistic disorder associated with an iso-dicentric Y chromosome. Dev Med Child Neurol 33:162–166Google Scholar
  10. Buchanan PD, Wyandt HE, D'Ercole AJ, Rao KW, Hartsell ML (1976) A mitotically unstable human dicentric Y chromosome in a male pseudohermaphrodite. Cytogenet Cell Genet 17:42–50Google Scholar
  11. Bühler EM, Frey R, Müller H, Voegelin M, Stalder GR (1971) Fluorescence pattern of a dicentric Y. Humangenetik 12:170–172Google Scholar
  12. Caspersson T, Lomakka G, Zech L (1971) The 24 fluorescence patterns of the human metaphase chromosomes: distinguishing characters and variability. Hereditas 67:89–102Google Scholar
  13. Chandley AC, Ambros P. McBeath S, Hargreave TB, Kilanowski F, Spowart G (1986) Short arm dicentric Y chromosome with associated statural defects in a sterile man. Hum Genet 73:350–353Google Scholar
  14. Chang HJ, Clark RD, Bachman H (1990) The phenotype of 45,X/46,XY mosaicism: an analysis of 92 prenatally diagnosed cases. Am J Hum Genet 46:156–167Google Scholar
  15. Chen H, Culley L (1992) Molecular studies of Y chromosome abnormalities using polymerase chain reaction (PCR). Am J Hum Genet 51 [Suppl]: A313Google Scholar
  16. Chieri PR de, Hirschhorn K (1979) Dicentric Y-chromosome mosaicism in a girl with clitoral hypertrophy. Hum Genet 52:149–152Google Scholar
  17. Cohen MM, MacGillivray MH, Capraro VJ, Aceto TA (1973) Human dicentric Y chromosomes: case report and review of the literature. J Med Genet 10:74–79Google Scholar
  18. Cooper C, Crolla JA, Laister C, Johnston DI, Cooke P (1991) An investigation of ring and dicentric chromosomes found in three Turner's syndrome patients using DNA analysis and in situ hybridisation with X and Y chromosome specific probes. J Med Genet 28:6–9Google Scholar
  19. Daniel A, Lyons N, Casey JH, Gras L (1980) Two dicentric Y isochromosomes, one without the Yqh heterochromatic segment. Review of the Y isochromosomes. Hum Genet 54:31–39Google Scholar
  20. Davis LG; Dibner MD, Battey JF (1986) Basic Methods in Molecular Biology, Elsevier Science Publishing Co., Inc., New York, N. Y.Google Scholar
  21. De Arce MA, Costigan C, Gosden JR, Lawler M, Humphries P (1992) Further evidence consistent with Yqh as an indicator of risk of gonadal blastoma in Y-bearing mosaic Turner syndrome. Clin Genet 41:28–32Google Scholar
  22. Dennis NR, Cockwell A, Clarke H, Crolla J (1990) Three males with structural abnormalities of the Y chromosome. J Med Genet 17:648Google Scholar
  23. Disteche CM, Saal H, Friedman C, Sybert V, Thuline H (1986a) Quantitative analysis of sex-chromosome mosaicism with X-Y DNA probes. Am J Hum Genet 38:751–758Google Scholar
  24. Disteche CM, Casanova M, Saal H, Friedman C, Sybert V, Graham J, Thuline H, Page DC, Fellous M (1986b) Small deletions of the short arm of the Y chromosome in 46,XY females. Proc Natl Acad Sci USA 83:7841–7844Google Scholar
  25. Drummond-Borg M, Pagon RA, Bradley CM, Nordlund J, Salk D (1988) Nonfluorescent dicentric Y in males with hypospadias. J Pediatr 113:469–473Google Scholar
  26. Fass B, Kaplan S, Lippe B, Sparkes RS (1978) Inconsistent expression of both centromeres of a dicentric Y chromosome in a child with ambiguous external genitalia. J Med Genet 15:232–236Google Scholar
  27. Feinberg AP, Vogelstein B (1983) A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132:6–13PubMedGoogle Scholar
  28. Frey RO, Bühler EM, Bühler UK, Stalder GR (1975) 45,X/ 46,XYq dic-Geschlechtschromosomenmosaik. Humangenetik 27:81–90Google Scholar
  29. Fryns JP, Kleczkowska A, Lemmens P, Van den Berghe H (1987) Unusual in vivo rearrangements of the Y-chromosome in two males. Clin Genet 31:132–136Google Scholar
  30. Fujimoto A, Boelter WD, Sparkes RS, Lin MS, Battersby K (1991) Monozygotic twins of discordant sex both with 45,X/46,X,idic(Y) mosaicism. Am J Med Genet 41:239–245Google Scholar
  31. Giraud F, Mattel JF, Lucas C, Mattel MG (1977) Four new cases of dicentric Y chromosomes. Hum Genet 36:249–260Google Scholar
  32. Gubbay J, Collignon J, Koopman P, Capel B, Economou A, Münsterberg A, Vivian N, Goodfellow P, Lovell-Badge R (1990) A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes. Nature 346:245–250Google Scholar
  33. Guttenbach M, Müller U, Schmid M (1990) Cytogenetic and molecular analysis of a Yq isochromosome. Hum Genet 86:147–150Google Scholar
  34. Haaf T, Schmid M (1990) Y isochromosome associated with a mosaic karyotype and inactivation of the centromere. Hum Genet85:486–490Google Scholar
  35. Hayek A, Yunis E (1975) Dicentric Y chromosome in mixed gonadal dysgenesis. J Med Genet 12:210–212Google Scholar
  36. Hermier M, Philippe N, Francois R (1979) Sujet masculin pubere et sans ambiguite genitale, 45X/46X dic(Yq): etude critique des particularites du phenotype. Arch Franc Pediatr 36:162–172Google Scholar
  37. Herva R, Saarinen I, Savikurki H, Chapelle A de la (1980) Dicentric Y chromosome arising via tandem translocation. Am J Med Genet 7:115–122Google Scholar
  38. Hsu LYF (1994) Phenotype/karyotype correlations of Y chromosome aneuploidy with emphasis on structural aberrations in postnatally diagnosed cases. Am J Med Genet 53:108–140Google Scholar
  39. Jäger RJ, Ebensperger C, Fraccaro M, Scherer G (1990) A ZFY-negative 46,XX true hermaphrodite is positive for the Y pseudoautosomal boundary. Hum Genet 85:666–668Google Scholar
  40. Johnston AW, Speed RM, Klopper A, Robinson JA (1974) A patient with a dicentric Y chromosome. Clin Genet 6:326–331Google Scholar
  41. King CR, Cook DM (1978) Bilateral gonadoblastoina in a phenotypic female with 45,X/46,X,dicentric iso Y [45,X/46,X,idic(Yq)] mosaicism. Birth Defects 14:109–122Google Scholar
  42. Koopman P, Gubbay J, Vivian N, Goodfellow P, Lovell-Badge R (1991) Male development of chromosomally female mice transgenic for SRY. Nature 351:117–121Google Scholar
  43. Kosztolanyi G (1988) Giemsa-11 technique elucidating three structurally altered nonfluorescent Y chromosomes: r(Y), idic (Yp), dir tan dup (Yp). Ann Genet 31:235–240Google Scholar
  44. Kovaleva NV, Yakovlev AF (1986) Morphology and mitotic condensation features of the human Y-chromosomes with structural reconstruction. Tsitologiia 28:1322–1328Google Scholar
  45. Kulikov RI, Mashkova MV, Verlinskaya DK, Bondarev GN (1976) Identification of some human chromosome aberration by the fluorescent method with quinacrine mustard. Tsitologiia 18(2): 213–218Google Scholar
  46. Lau Y-FC, Chan K (1989) The putative testis-determining factor and related genes are expressed as discrete-sized transcripts in adult gonadal and somatic tissues. Am J Hum Genet 45:942–952Google Scholar
  47. Lau Y-F, Huang JC, Dozy AM, Kan YW (1984) A rapid screening test for antenatal sex determination. Lancet 1:14–16Google Scholar
  48. Magenis RE, Brown MG, Donlon T, Olson SB, Sheehy R, Tomar D (1985) Structural aberrations of the Y chromosome, including the nonfluorescent Y: cytologic origin and consequences. In: Sandberg AA (ed) The Y chromosome, part A: basic characteristics of the Y chromosome. (Progress and topics in cytogenetics, vol 6) Alan R. Liss. Inc. New York, pp 537–574Google Scholar
  49. Magenis RE, Casanova M, Fellous M, Olson S, Sheehy R (1987) Further cytologic evidence for Xp-Yp translocation in XX males using in situ hybridization with Y-derived probe. Hum Genet 75:228–233Google Scholar
  50. Málkov J, Chrz R, Motlík K, Stárka L, Kobilková J, ŠilinkováMálková E (1974) 46,XX gonadal dysgenesis and ovarian hypoplasia. Humangenetik 23:205–211Google Scholar
  51. Maraschio P, Zuffardi O, Caiulo A, Dainotti E, Piantanida M, Rivera H, Tupler R (1990) Deletion of specific sequences or modification of centromeric chromatin are responsible for Y chromosome centromere inactivation. Hum Genet 85:491–494Google Scholar
  52. Mićić M, Mićić S, Babić M, Diklić V (1990) Phenotype of two males with abnormal Y chromosomes. Clin Genet 37:321–326Google Scholar
  53. Morillo-Cucci G, German J (1971) Abnormal Y chromosomes and monosomy 45,X: A concept derived from the study of three patients. Birth Defects 7:210–214Google Scholar
  54. Müller U, Donlon T, Schmid M, Fitch N, Richer C-L, Lalande M, Latt SA (1986) Deletion mapping of the testis determining locus with DNA probes in 46,XX males and in 46,XY and 46,X,dic(Y) females. Nucleic Acids Res 14:6489–6505Google Scholar
  55. Nanko S, Konishi T, Satoh S, Ikeda H (1993) A case of schizophrenia with a dicentric Y chromosome. Jpn J Hum Genet 38:229–232Google Scholar
  56. Page DC (1987) Hypothesis: a Y-chromosomal gene causes gonadoblastoma in dysgenetic gonads. Development 101 [Suppl]:151–155Google Scholar
  57. Page DC, Mosher R, Simpson EM, Fisher EMC, Mardon G, Pollack J, McGillivray B, Chapelle A de la, Brown LG (1987) The sex-determining region of the human Y chromosome encodes a finger protein. Cell 51:1091–1104Google Scholar
  58. Petrovic V, Nasioulas S, Chow CW, Voullaire L, Schmidt M, Dahl H (1992) Minute Y chromosome derived marker in a child with gonadoblastoma: cytogenetic and DNA studies. J Med Genet 29:542–546Google Scholar
  59. Plauchu H, Magnin G, Laurent C, Combet A, Drapier E, Dumont M, Rochet Y, Robert JM (1981) Dysgénésie gonadique et chromosome Y dicentrique: rapport de deux cas dont un avec gonadoblastome. J Gynecol Obstet Biol Reprod 10:839–844Google Scholar
  60. Polani PE, Alberman E, Alexander BJ, Benson PF, Berry AC, Blunt S, Daker MG, Fensom AH, Garrett DM, McGuire VM, Roberts JAF, Seller MJ, Singer JD (1979) Sixteen years' experience of counselling, diagnosis, and prenatal detection in one Genetic Centre: progress, results, and problems. J Med Genet16:166–175Google Scholar
  61. Ponzio G, DeMarchi M, Carbonara A, Godano A, Massara F (1981) Dicentric Y chromosome in a patient with gonadal dysgenesis and seminoma. Hum Genet 58:282–284Google Scholar
  62. Proto G, Bartolomei P, Mazzolini A, Grimaldi F, Torossi I, Bertolissi F (1991) Disgenesia gonadica mista (DGM): descrizione di un caso. Minerva Endocrinol 16:203–206Google Scholar
  63. Rappold GA (1993) The pseudoautosomal regions of the human sex chromosomes. Hum Genet 92:315–324Google Scholar
  64. Rasheed BKA, Whisenant EC, Fernandez R, Ostrer H, Bhatnagar YM (1991) A Y-chromosomal DNA fragment is conserved in human and chimpanzee. Mol Biol Evol 8:416–432Google Scholar
  65. Roubin M, Grouchy J de, Chauveau P, Rappaport R, Pellerin D (1977) Chromosome Y dicentrique chez un pseudo-hermaphrodite masculin, [45,X/46,X,dic(Y)/47,XYY]. Ann Genet 20:185–189Google Scholar
  66. Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NYGoogle Scholar
  67. Savary JB, Vasseur F, Flactif M, Willatt L, Lefebvre J, FergusonSmith MA, Deminatti MM (1992) Cytogenetic and molecular investigations of an abnormal Y chromosome: evidence for a pseudo-dicentric (Yq) isochromosome. Ann Genet 35:134–139Google Scholar
  68. Schmid W, D'Apuzzo V (1978) Centromere inactivation in a case of Turner variant with two dicentric iso-long arm Y chromosomes. Hum Genet 41:217–223Google Scholar
  69. Seabright M (1971) A rapid banding technique for human chromosomes. Lancet 11:971–972Google Scholar
  70. Seifer DB, Meyers-Seifer CH, Lavy G, Genel M, DeCherney AH, Yang-Feng TL (1991) Laparoscopic adnexectomy in a prepubertal Turner mosaic female with isodicentric Y. Hum Reprod6:566–567Google Scholar
  71. Siebers JW, Vogel W, Hepp H, Bolze H, Dittrich A (1973) Structural aberrations of the Y chromosome and the corresponding phenotype: report of a case with the karyotype 45,X/46,X, i(Yp). Humangenetik 19:57–66Google Scholar
  72. Sinclair AH, Berta P, Palmer MS, Hawkins JR, Griffiths BL, Smith MJ, Foster JW, Frischauf A-M, Lovell-Badge R, Goodfellow PN (1990) A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature 346:240–244Google Scholar
  73. Sloan MS, Rosenberg SM, Brown JA (1984) Primary amenorrhea and virilization in a true hermaphrodite with a rare dicentric Y chromosome. Obstet Gynecol 64:64S-67SGoogle Scholar
  74. Speleman F, Van der Auwera B, Mangelschots K, Vercruyssen M, Raap T, Wiegant J, Craen M, Leroy J (1990) Identification and characterization of normal length nonfluorescent Y chromosomes: cytogenetic analysis, Southern hybridization and nonisotopic in situ hybridization. Hum Genet 85:569–575Google Scholar
  75. Stalvey JRD, Erickson RP, Dasouki M, Glover T, Shokir M (1988) Clarification of chromosomal abnormalities associated with sexual ambiguity by studies with Y-chromosomal DNA sequences. Cytogenet Cell Genet 47:140–143Google Scholar
  76. Stevenson AC, Bedford J, Barberton GM (1971) A patient with 45,X/46,XXq-/46,XXq-dic karyotype. J Med Genet 8:513–516Google Scholar
  77. Sumner AT (1972) A simple technique for demonstrating centromeric heterochromatin. Exp Cell Res 75:304–306PubMedGoogle Scholar
  78. Takihara H, Tsukahara M, Baba Y, Naito K, Kajii T (1993) Dicentric Y chromosome in azoospermic males. Br J Urol 71:596–599Google Scholar
  79. Taniuchi I, Mizutani S, Namiki M, Okuyama A, Kodama M (1991) Short-arm dicentric Y chromosome in a sterile man: a case report. J Urol 146:415–416Google Scholar
  80. Tuncbilek E, Halicioglu C, Bobrow M, Ustay K (1976) 45,XO/ 46,XYq dic mosaicism in a patient with ambiguous genitalia. Clin Genet 9:365–370Google Scholar
  81. Weckworth PF, Johnson HW, Pantzar JT, Coleman GU, Masterson JST, McGillivray B, Tze WJ (1988) Dicentric Y chromosome and mixed dysgenesis. J Urol 139:91–94Google Scholar
  82. Whisenant EC, Rasheed BKA, Ostrer H, Bhatnagar YM (1991) Evolution and sequence analysis of a human Y-chromosomal DNA fragment. J Mol Evol 33:133–141Google Scholar
  83. Wolfe J, Darling SM, Erickson RP, Craig R, Willard HF, Goodfellow PN (1985) Isolation and characterization of an alphoid centromeric repeat family from the human Y chromosome. J Mol Biol 182:477–485Google Scholar
  84. Ying KL, Ives EJ (1971) Mitotic behavior of a human dicentric Y chromosome. Cytogenetics 10:208–218Google Scholar
  85. Ying KL, Ives EJ, Stephenson OD (1977) Gonadal dysgenesis with 45,X/46,X,dic(Yp) mosaicism. Clin Genet 11:402–408Google Scholar
  86. Yunis JJ, Sawyer JR, Ball DW (1978) The characterization of high-resolution G-banded chromosomes of man. Chromosoma 67:293–307Google Scholar

Copyright information

© Springer-Verlag 1995

Authors and Affiliations

  • Cathy M. Tuck-Muller
    • 1
  • Harold Chen
    • 1
  • José E. Martínez
    • 1
  • Chuen-Cheh Shen
    • 1
  • Shibo Li
    • 1
  • Christine Kusyk
    • 1
  • Denise A. S. Batista
    • 3
  • Yogendra M. Bhatnagar
    • 1
  • Edmund Dowling
    • 2
  • Wladimir Wertelecki
    • 1
  1. 1.Department of Medical GeneticsUniversity of South AlabamaMobileUSA
  2. 2.Department of PathologyUniversity of South AlabamaMobileUSA
  3. 3.Department of Gynecology and ObstetricsUnion Memorial HospitalBaltimoreUSA

Personalised recommendations