Journal of Autism and Developmental Disorders

, Volume 43, Issue 3, pp 530–539 | Cite as

Identification of Expanded Alleles of the FMR1 Gene in the CHildhood Autism Risks from Genes and Environment (CHARGE) Study

  • Flora TassoneEmail author
  • Nimrah S. Choudhary
  • Federica Tassone
  • Blythe Durbin-Johnson
  • Robin Hansen
  • Irva Hertz-Picciotto
  • Isaac PessahEmail author
Original Paper


Fragile X syndrome (FXS) is a neuro-developmental disorder characterized by intellectual disabilities and autism spectrum disorders (ASD). Expansion of a CGG trinucleotide repeat (>200 repeats) in the 5′UTR of the fragile X mental retardation gene, is the single most prevalent cause of cognitive disabilities. Several screening studies for FXS, among individuals with ID from different ethnic populations, have indicated that the prevalence of the syndrome varies between 0.5 and 16 %. Because the high co-morbidity with autism, we have conducted a screening study of the cohort from CHARGE, a large-scale, population-based, case control study. We have identified six subjects carrying an expanded allele, which emphasize the importance of screening for FXS in a population with intellectual disabilities and ASD.


Autism spectrum disorder Developmental delay Fragile X Premutation Screening CGG 



A particular thanks to the families participating in the CHARGE study. This work was supported by the National Institutes of Health [HD02274], matching funds for the CHARGE study, and by R01-ES015359, P01ES011269 from the National Institute of Environmental Health Sciences and Award Numbers R833292 and R829388 from the Environmental Protection Agency. The project described was also supported by the National Center for Research Resources, National lnstitutes of Health, through grant #UL1 RR024146. This work is dedicated to the memory of Matteo.

Supplementary material

10803_2012_1580_MOESM1_ESM.doc (198 kb)
Supplementary material 1 (DOC 197 kb)
10803_2012_1580_MOESM2_ESM.doc (198 kb)
Supplementary material 2 (DOC 197 kb)


  1. Aziz, M., Stathopulu, E., Callias, M., Taylor, C., Turk, J., Oostra, B., et al. (2003). Clinical features of boys with fragile X premutations and intermediate alleles. American Journal of Medical Genetics, 121B(1), 119–127.PubMedCrossRefGoogle Scholar
  2. Bailey, A., Bolton, P., Butler, L., Le Couteur, A., Murphy, M., Scott, S., et al. (1993). Prevalence of the fragile X anomaly amongst autistic twins and singletons. J of Child Psychology and Psychiatry, 34(5), 673–688.CrossRefGoogle Scholar
  3. Bailey, D. B., Jr, Hatton, D. D., Mesibov, G. B., Ament, N., & Skinner, M. (2000). Early development, temperament and functional impairment in autism and fragile X syndrome. Journal of Autism and Developmental Disorders, 30(1), 49–59.PubMedCrossRefGoogle Scholar
  4. Bailey, D. B., Jr, Hatton, D. D., Skinner, M., & Mesibov, G. B. (2001). Autistic behavior, FMR1 protein, and developmental trajectories in young males with fragile X syndrome. Journal of Autism and Developmental Disorder, 31(2), 165–174.CrossRefGoogle Scholar
  5. Bailey, D. B., Jr., Raspa, M., Olmsted, M., & Holiday, D. B. (2008). Co-occurring conditions associated with FMR1 gene variations: Findings from a national parent survey. American Journal of Medical Genetics, Part A, 146A(16), 2060–2069.CrossRefGoogle Scholar
  6. Biancalana, V., Beldjord, C., Taillandier, A., Szpiro-Tapia, S., Cusin, V., Gerson, F., et al. (2004). Five years of molecular diagnosis of Fragile X syndrome (1997–2001): A collaborative study reporting 95 % of the activity in France. American Journal of Medical Genetics, 129A(3), 218–224.PubMedCrossRefGoogle Scholar
  7. Blomquist, H. K., Bohman, M., Edvinsson, S. O., Gillberg, C., Gustavson, K. H., Holmgren, G., et al. (1985). Frequency of the fragile X syndrome in infantile autism: A Swedish multicenter study. Clinical Genetics, 27(2), 113–117.PubMedCrossRefGoogle Scholar
  8. Bodega, B., Bione, S., Dalpra, L., Toniolo, D., Ornaghi, F., Vegetti, W., et al. (2006). Influence of intermediate and uninterrupted FMR1 CGG expansions in premature ovarian failure manifestation. Human Reproduction, 21(4), 952–957.PubMedCrossRefGoogle Scholar
  9. Bourgeois, J. A., Coffey, S. M., Rivera, S. M., Hessl, D., Gane, L. W., Tassone, F., et al. (2009). A review of fragile X premutation disorders: Expanding the psychiatric perspective. Journal of Clinical Psychiatry, 70(6), 852–862.PubMedCrossRefGoogle Scholar
  10. Bretherick, K. L., Fluker, M. R., & Robinson, W. P. (2005). FMR1 repeat sizes in the gray zone and high end of the normal range are associated with premature ovarian failure. Human Genetics, 117(4), 376–382.PubMedCrossRefGoogle Scholar
  11. Brown, W. T., Jenkins, E. C., Cohen, I. L., Fisch, G. S., Wolf-Schein, E. G., Gross, A., et al. (1986). Fragile X and autism: A multicenter survey. American Journal of Medical Genetics, 23(1–2), 341–352.PubMedCrossRefGoogle Scholar
  12. Chen, L., Hadd, A., Sah, S., Filipovic-Sadic, S., Krosting, J., Sekinger, E., et al. (2010). An information-rich CGG repeat primed PCR that detects the full range of fragile X expanded alleles and minimizes the need for southern blot analysis. Journal of Molecular Diagnostics, 12(5), 589–600.PubMedCrossRefGoogle Scholar
  13. Chonchaiya, W., Au, J., Schneider, A., Hessl, D., Harris, S. W., Laird, M., Mu, Y., Tassone, F., Nguyen, D. V., & Hagerman, R. J. (2012). Increased prevalence of seizures in boys who were probands with the FMR1 premutation and co-morbid autism spectrum disorder. Human Genetics, 131(4), 581–589. doi: 10.1007/s00439-011-1106-6 PubMedCrossRefGoogle Scholar
  14. Clifford, S., Dissanayake, C., Bui, Q. M., Huggins, R., Taylor, A. K., & Loesch, D. Z. (2007). Autism spectrum phenotype in males and females with fragile X full mutation and premutation. Journal of Autism and Developmental Disorders, 37(4), 738–747.PubMedCrossRefGoogle Scholar
  15. Cronister, A., Schreiner, R., Wittenberger, M., Amiri, K., Harris, K., & Hagerman, R. J. (1991). Heterozygous fragile X female: Historical, physical, cognitive, and cytogenetic features. American Journal of Medical Genetics, 38(2–3), 269–274.PubMedCrossRefGoogle Scholar
  16. de Vries, B. B., Mohkamsing, S., van den Ouweland, A. M., Halley, D. J., Niermeijer, M. F., Oostra, B. A., et al. (1998). Screening with the FMR1 protein test among mentally retarded males. Human Genetics, 103(4), 520–522.PubMedCrossRefGoogle Scholar
  17. de Vries, B. B., van den Ouweland, A. M., Mohkamsing, S., Duivenvoorden, H. J., Mol, E., Gelsema, K., et al. (1997). Screening and diagnosis for the fragile X syndrome among the mentally retarded: An epidemiological and psychological survey. Collaborative Fragile X Study Group. American Journal of Human Genetics, 61(3), 660–667.PubMedCrossRefGoogle Scholar
  18. Dombrowski, C., Levesque, M. L., Morel, M. L., Rouillard, P., Morgan, K., & Rousseau, F. (2002). Premutation and intermediate-size FMR1 alleles in 10 572 males from the general population: Loss of an AGG interruption is a late event in the generation of fragile X syndrome alleles. Human Molecular Genetics, 11(4), 371–378.PubMedCrossRefGoogle Scholar
  19. Farzin, F., Perry, H., Hessl, D., Loesch, D., Cohen, J., Bacalman, S., et al. (2006). Autism spectrum disorders and attention-deficit/hyperactivity disorder in boys with the fragile X premutation. Journal of Developmental and Behavioral Pediatrics, 27(2 Suppl), S137–S144.PubMedCrossRefGoogle Scholar
  20. Fatemi, S. H., & Folsom, T. D. (2011). The role of fragile X mental retardation protein in major mental disorders. Neuropharmacology, 60(7–8), 1221–1226.PubMedCrossRefGoogle Scholar
  21. Fatemi, S. H., Kneeland, R. E., Liesch, S. B., & Folsom, T. D. (2010). Fragile X mental retardation protein levels are decreased in major psychiatric disorders. Schizophrenia Research, 124(1–3), 246–247.PubMedCrossRefGoogle Scholar
  22. Fernandez-Carvajal, I., Walichiewicz, P., Xiaosen, X., Pan, R., Hagerman, P. J., & Tassone, F. (2009). Screening for expanded alleles of the FMR1 gene in blood spots from newborn males in a Spanish population. Journal of Molecular Diagnostics, 11(4), 324–329.PubMedCrossRefGoogle Scholar
  23. Filipovic-Sadic, S., Sah, S., Chen, L., Krosting, J., Sekinger, E., Zhang, W., et al. (2010). A novel FMR1 PCR method for the routine detection of low-abundance expanded alleles and full mutations in fragile X syndrome. Clinical Chemistry, 56(3), 399–408.PubMedGoogle Scholar
  24. Fu, Y. H., Kuhl, D. P., Pizzuti, A., Pieretti, M., Sutcliffe, J. S., Richards, S., et al. (1991). Variation of the CGG repeat at the fragile X site results in genetic instability: Resolution of the Sherman paradox. Cell, 67(6), 1047–1058.PubMedCrossRefGoogle Scholar
  25. Garcia-Nonell, C., Ratera, E. R., Harris, S., Hessl, D., Ono, M. Y., Tartaglia, N., et al. (2008). Secondary medical diagnosis in fragile X syndrome with and without autism spectrum disorder. American Journal of Medical Genetics, Part A, 146A(15), 1911–1916.CrossRefGoogle Scholar
  26. Haddad, L. A., Aguiar, M. J., Costa, S. S., Mingroni-Netto, R. C., Vianna-Morgante, A. M., & Pena, S. D. (1999). Fully mutated and gray-zone FRAXA alleles in Brazilian mentally retarded boys. American Journal of Medical Genetics, 84(3), 198–201.PubMedCrossRefGoogle Scholar
  27. Hagerman, P. J. (2002). Gene expression and molecular approaches to therapy. In R. J. Hagerman & P. J. Hagerman (Eds.), Fragile X syndrome: Diagnosis, treatment and research (3rd ed.). Baltimore, MD: The Johns Hopkins University Press.Google Scholar
  28. Hagerman, R. J., Leehey, M., Heinrichs, W., Tassone, F., Wilson, R., Hills, J., et al. (2001). Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X. Neurology, 57, 127–130.PubMedCrossRefGoogle Scholar
  29. Hagerman, R. J., Rivera, S. M., & Hagerman, P. J. (2008). The fragile X family of disorders: A model for autism and targeted treatments. Current Pediatric Reviews, 4, 40–52.CrossRefGoogle Scholar
  30. Hall, D. A., Berry-Kravis, E., Zhang, W., Tassone, F., Spector, E., Zerbe, G., et al. (2011). FMR1 gray-zone alleles: association with Parkinson’s disease in women? Movement Disorders: Official Journal of the Movement Disorder Society, 26(10), 1900–1906.CrossRefGoogle Scholar
  31. Harris, S. W., Hessl, D., Goodlin-Jones, B., Ferranti, J., Bacalman, S., Barbato, I., et al. (2008). Autism profiles of males with fragile X syndrome. American Journal of Mental Retardation, 113(6), 427–438.PubMedCrossRefGoogle Scholar
  32. Hatton, D., Bailey, D. B., Roberts, J., Skinner, M., Mayher, L., Duffee Clark, R., et al. (2000). Early intervention services for young boys with fragile X syndrome. Journal of Early Intervention, 23(4), 235–251.CrossRefGoogle Scholar
  33. Hatton, D. D., Sideris, J., Skinner, M., Mankowski, J., Bailey, D. B., Jr, Roberts, J. E., et al. (2006). Autistic behavior in children with fragile X syndrome: Prevalence, stability, and the impact of FMRP. American Journal of Medical Genetics, Part A, 140(17), 1804–1813.CrossRefGoogle Scholar
  34. Hecimovic, S., Tarnik, I. P., Baric, I., Cakarun, Z., & Pavelic, K. (2002). Screening for fragile X syndrome: Results from a school for mentally retarded children. Acta Paediatrica, 91(5), 535–539.PubMedCrossRefGoogle Scholar
  35. Hertz-Picciotto, I., Croen, L. A., Hansen, R., Jones, C. R., van de Water, J., & Pessah, I. N. (2006). The CHARGE study: An epidemiologic investigation of genetic and environmental factors contributing to autism. Environmental Health Perspectives, 114(7), 1119–1125.PubMedCrossRefGoogle Scholar
  36. Hessl, D., Tassone, F., Loesch, D. Z., Berry-Kravis, E., Leehey, M. A., Gane, L. W., et al. (2005). Abnormal elevation of FMR1 mRNA is associated with psychological symptoms in individuals with the fragile X premutation. American Journal of Medical Genetics Part B Neuropsychiatric Genetics, 139(1), 115–121.CrossRefGoogle Scholar
  37. Iong, K., Tong, T., Gane, L., Sorensen, P., Berry-Kravis, E., Nguyen, D., Mu, Y., Skinner, D., Bailey, D., Hagerman, R., & Tassone, F. (2011). Newborn screening in fragile X syndrome: prevalence and allele distribution of the FMR1 gene. Paper presented at the American College Medical Genetics, Vancouver.Google Scholar
  38. Jacquemont, S., Hagerman, R. J., Leehey, M., Grigsby, J., Zhang, L., Brunberg, J. A., et al. (2003). Fragile X premutation tremor/ataxia syndrome: Molecular, clinical, and neuroimaging correlates. American Journal of Human Genetics, 72(4), 869–878.PubMedCrossRefGoogle Scholar
  39. Kau, A. S. M., Tierney, E., Bukelis, I., Stump, M. H., Kates, W. R., Trescher, W. H., et al. (2004). Social behavior profile in young males with fragile X syndrome: Characteristics and specificity. American Journal of Medical Genetics, 126A, 9–17.PubMedCrossRefGoogle Scholar
  40. Lachiewicz, A. M., & Dawson, D. V. (1994). Behavior problems of young girls with fragile X syndrome: Factor scores on the Conners’ Parent’s Questionnaire. American Journal of Medical Genetics, 51(4), 364–369.PubMedCrossRefGoogle Scholar
  41. Lewis, P., Abbeduto, L., Murphy, M., Richmond, E., Giles, N., Bruno, L., et al. (2006). Cognitive, language and social-cognitive skills of individuals with fragile X syndrome with and without autism. Journal of Intellectual Disability Research, 50(Pt 7), 532–545.PubMedCrossRefGoogle Scholar
  42. Loesch, D. Z., Bui, Q. M., Dissanayake, C., Clifford, S., Gould, E., Bulhak-Paterson, D., et al. (2007). Molecular and cognitive predictors of the continuum of autistic behaviours in fragile X. Neuroscience and Biobehavioral Reviews, 31(3), 315–326.PubMedCrossRefGoogle Scholar
  43. Loesch, D. Z., Godler, D. E., Khaniani, M., Gould, E., Gehling, F., Dissanayake, C., et al. (2009). Linking the FMR1 alleles with small CGG expansions with neurodevelopmental disorders: Preliminary data suggest an involvement of epigenetic mechanisms. American Journal of Medical Genetics, Part A, 149A(10), 2306–2310.CrossRefGoogle Scholar
  44. Lord, C., Risi, S., Lambrecht, L., Cook, E. H., Jr, Leventhal, B. L., DiLavore, P. C., et al. (2000). The Autism Diagnostic Observation Schedule-Generic: A standard measure of social and communication deficits associated with the spectrum of autism. Journal of Autism and Developmental Disorder, 30(3), 205–223.CrossRefGoogle Scholar
  45. Lord, C., Rutter, M., & Le Couteur, A. (1994). Autism Diagnostic Interview-Revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders. Journal of Autism and Developmental Disorders, 24(5), 659–685.PubMedCrossRefGoogle Scholar
  46. Maddalena, A., Richards, C. S., McGinniss, M. J., Brothman, A., Desnick, R. J., Grier, R. E., et al. (2001). Technical standards and guidelines for fragile X: The first of a series of disease-specific supplements to the Standards and Guidelines for Clinical Genetics Laboratories of the American College of Medical Genetics. Quality Assurance Subcommittee of the Laboratory Practice Committee. Genetic Medicine, 3(3), 200–205.CrossRefGoogle Scholar
  47. Major, T., Culjkovic, B., Stojkovic, O., Gucscekic, M., Lakic, A., & Romac, S. (2003). Prevalence of the fragile X syndrome in Yugoslav patients with non-specific mental retardation. Journal of Neurogenetics, 17(2–3), 223–230.PubMedGoogle Scholar
  48. Mazzocco, M. M., Kates, W. R., Baumgardner, T. L., Freund, L. S., & Reiss, A. L. (1997). Autistic behaviors among girls with fragile X syndrome. Journal of Autism and Developmental Disorder, 27(4), 415–435.CrossRefGoogle Scholar
  49. Mila, M., Sanchez, A., Badenas, C., Brun, C., Jimenez, D., Villa, M. P., et al. (1997). Screening for FMR1 and FMR2 mutations in 222 individuals from Spanish special schools: Identification of a case of FRAXE-associated mental retardation. Human Genetics, 100, 503–507.PubMedCrossRefGoogle Scholar
  50. Miller, L. J., McIntosh, D. N., McGrath, J., Shyu, V., Lampe, M., Taylor, A. K., et al. (1999). Electrodermal responses to sensory stimuli in individuals with fragile X syndrome: A preliminary report. American Journal of Medical Genetics, 83(4), 268–279.PubMedCrossRefGoogle Scholar
  51. Mullen, E. M. (1995). Mullen Scales of Early Learning. Circle Pines: American Guidance Service.Google Scholar
  52. Murray, A., Youings, S., Dennis, N., Latsky, L., Linehan, P., McKechnie, N., et al. (1996). Population screening at the FRAXA and FRAXE loci: Molecular analyses of boys with learning difficulties and their mothers. Human Molecular Genetics, 5(6), 727–735.PubMedCrossRefGoogle Scholar
  53. Pandey, U. B., Phadke, S., & Mittal, B. (2002). Molecular screening of FRAXA and FRAXE in Indian patients with unexplained mental retardation. Genetic Testing, 6(4), 335–339.PubMedCrossRefGoogle Scholar
  54. Patsalis, P. C., Sismani, C., Hettinger, J. A., Boumba, I., Georgiou, I., Stylianidou, G., et al. (1999). Molecular screening of fragile X (FRAXA) and FRAXE mental retardation syndromes in the Hellenic population of Greece and Cyprus: incidence, genetic variation, and stability. American Journal of Medical Genetics, 84(3), 184–190.PubMedCrossRefGoogle Scholar
  55. Pieretti, M., Zhang, F. P., Fu, Y. H., Warren, S. T., Oostra, B. A., Caskey, C. T., et al. (1991). Absence of expression of the FMR-1 gene in fragile X syndrome. Cell, 66(4), 817–822.PubMedCrossRefGoogle Scholar
  56. Pouya, A. R., Abedini, S. S., Mansoorian, N., Behjati, F., Nikzat, N., Mohseni, M., et al. (2009). Fragile X syndrome screening of families with consanguineous and non-consanguineous parents in the Iranian population. European Journal of Medical Genetics, 52(4), 170–173.PubMedCrossRefGoogle Scholar
  57. Reddy, K. S. (2005). Cytogenetic abnormalities and fragile-X syndrome in Autism Spectrum Disorder. BMC Medical Genetics, 6(1), 3.PubMedCrossRefGoogle Scholar
  58. Roberts, J. E., Bailey, D. B., Jr, Mankowski, J., Ford, A., Sideris, J., Weisenfeld, L. A., et al. (2009). Mood and anxiety disorders in females with the FMR1 premutation. American Journal of Medical Genetics, Part B Neuropsychiatric Genetics, 150B(1), 130–139.CrossRefGoogle Scholar
  59. Rogers, S. J., Wehner, E. A., & Hagerman, R. J. (2001). The behavioral phenotype in fragile X: Symptoms of autism in very young children with fragile X syndrome, idiopathic autism, and other developmental disorders. Journal of Developmental and Behavioral Pediatrics, 22(6), 409–417.PubMedCrossRefGoogle Scholar
  60. Rousseau, F., Rouillard, P., Morel, M. L., Khandjian, E. W., & Morgan, K. (1995). Prevalence of carriers of premutation-size alleles of the FMRI gene—and implications for the population genetics of the fragile X syndrome. American Journal of Human Genetics, 57(5), 1006–1018.PubMedGoogle Scholar
  61. Rutter, M., Bailey, A., Berument, S. K., Lord, C., & Pickles, A. (2003). Social Communication Questionnaire (SCQ). Los Angeles: Western Psychological Services.Google Scholar
  62. Schaefer, G. B., & Lutz, R. E. (2006). Diagnostic yield in the clinical genetic evaluation of autism spectrum disorders. Genetic Medicine, 8(9), 549–556.Google Scholar
  63. Sharma, D., Gupta, M., & Thelma, B. K. (2001). Expansion mutation frequency and CGG/GCC repeat polymorphism in FMR1 and FMR2 genes in an Indian population. Genetic Epidemiology, 20(1), 129–144.PubMedCrossRefGoogle Scholar
  64. Sherman, S. L. (2000). Premature ovarian failure in the fragile X syndrome. American Journal of Medical Genetics (Seminars in Medical Genetics), 97(3), 189–194.CrossRefGoogle Scholar
  65. Sparrow, S. S., Balla, D. A., & Cicchetti, D. V. (1984). Vineland Adaptive Behavior Scales Survey Form Manual. Circle Pines: American Guidance Service.Google Scholar
  66. Sudhalter, V., Cohen, I. L., Silverman, W., & Wolf-Schein, E. G. (1990). Conversational analyses of males with fragile X, Down syndrome, and autism: Comparison of the emergence of deviant language. American Journal of Mental Retardation, 94(4), 431–441.PubMedGoogle Scholar
  67. Sullivan, A. K., Crawford, D. C., Scott, E. H., Leslie, M. L., & Sherman, S. L. (2002). Paternally transmitted FMR1 alleles are less stable than maternally transmitted alleles in the common and intermediate size range. American Journal of Human Genetics, 70(6), 1532–1544.PubMedCrossRefGoogle Scholar
  68. Sullivan, A. K., Marcus, M., Epstein, M. P., Allen, E. G., Anido, A. E., Paquin, J. J., et al. (2005). Association of FMR1 repeat size with ovarian dysfunction. Human Reproduction, 20(2), 402–412.PubMedCrossRefGoogle Scholar
  69. Syrrou, M., Georgiou, I., Grigoriadou, M., Petersen, M. B., Kitsiou, S., Pagoulatos, G., et al. (1998). FRAXA and FRAXE prevalence in patients with nonspecific mental retardation in the Hellenic population. Genetic Epidemiology, 15(1), 103–109.PubMedCrossRefGoogle Scholar
  70. Tassone, F., Hagerman, R. J., Chamberlain, W. D., & Hagerman, P. J. (2000). Transcription of the FMR1 gene in individuals with fragile X syndrome. American Journal of Medical Genetics (Seminars in Medical Genetics), 97(3), 195–203.CrossRefGoogle Scholar
  71. Tassone, F., Pan, R., Amiri, K., Taylor, A. K., & Hagerman, P. J. (2008). A rapid polymerase chain reaction-based screening method for identification of all expanded alleles of the fragile X (FMR1) gene in newborn and high-risk populations. Journal of Molecular Diagnostics, 10(1), 43–49.PubMedCrossRefGoogle Scholar
  72. Toledano-Alhadef, H., Basel-Vanagaite, L., Magal, N., Davidov, B., Ehrlich, S., Drasinover, V., et al. (2001). Fragile-X carrier screening and the prevalence of premutation and full-mutation carriers in Israel. American Journal of Human Genetics, 69(2), 351–360.PubMedCrossRefGoogle Scholar
  73. Verkerk, A. J., Pieretti, M., Sutcliffe, J. S., Fu, Y. H., Kuhl, D. P., Pizzuti, A., et al. (1991). Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell, 65(5), 905–914.PubMedCrossRefGoogle Scholar
  74. Watson, M. S., Breg, W. R., Hobbins, J. C., & Mahoney, M. J. (1984). Cytogenetic diagnosis using midtrimester fetal blood samples: Application to suspected mosaicism and other diagnostic problems. American Journal of Medical Genetics, 19(4), 805–813.PubMedCrossRefGoogle Scholar
  75. Wittenberger, M. D., Hagerman, R. J., Sherman, S. L., McConkie-Rosell, A., Welt, C. K., Rebar, R. W., et al. (2007). The FMR1 premutation and reproduction. Fertility and Sterility, 87(3), 456–465.PubMedCrossRefGoogle Scholar
  76. Yrigollen, C. M., Durbin-Johnson, B., Gane, L., Nelson, D. L., Hagerman, R., Hagerman, P. J., & Tassone, F. (2012). AGG interruptions within the maternal FMR1 gene reduce the risk of offspring with fragile X syndrome. Genetics in Medicine. doi: 10.1038/gim.2012.34
  77. Yrigollen, C. M., Tassone, F., & Durbin-Johnson, B. (2011). The role of AGG interruptions in the transcription of FMR1 premutation alleles. PLoS One, 6(7), e21728.PubMedCrossRefGoogle Scholar
  78. Yu, S., Pritchard, M., Kremer, E., Lynch, M., Nancarrow, J., Baker, E., et al. (1991). Fragile X genotype characterized by an unstable region of DNA. Science, 252(5010), 1179–1181.CrossRefGoogle Scholar
  79. Yuhas, J., Walichiewicz, P., Pan, R., Zhang, W., Casillas, E. M., Hagerman, R. J., et al. (2009). High-risk fragile x screening in Guatemala: Use of a new blood spot polymerase chain reaction technique. Genetic Testing and Molecular Biomarkers, 13(6), 855–859.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Flora Tassone
    • 1
    • 2
    Email author
  • Nimrah S. Choudhary
    • 1
  • Federica Tassone
    • 1
  • Blythe Durbin-Johnson
    • 3
  • Robin Hansen
    • 2
    • 4
  • Irva Hertz-Picciotto
    • 2
    • 3
    • 5
  • Isaac Pessah
    • 2
    • 6
    • 5
    Email author
  1. 1.Department of Biochemistry and Molecular Medicine, School of MedicineUniversity of California, DavisSacramentoUSA
  2. 2.MIND InstituteUniversity of California Davis Health SystemSacramentoUSA
  3. 3.Department of Public Health Sciences, School of MedicineUniversity of California, DavisDavisUSA
  4. 4.Department of Pediatrics, School of MedicineUniversity of California, DavisSacramentoUSA
  5. 5.UC Davis Center for Children’s Environmental Health and Disease PreventionUniversity of California, DavisDavisUSA
  6. 6.Department of Molecular Biosciences, School of Veterinary MedicineUniversity of California, DavisDavisUSA

Personalised recommendations