Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-8448b6f56d-qsmjn Total loading time: 0 Render date: 2024-04-18T23:03:32.975Z Has data issue: false hasContentIssue false

1 - Intergenerational effects of mutations in the fragile X mental retardation 1 gene. Fragile X: A model of X-linked mental retardation and neurodegeneration

Published online by Cambridge University Press:  04 August 2010

By
Mariya Borodyanskaya ,
Sarah Coffey ,
Michele Y. Ono  and
Randi J. Hagerman
Edited by
Marcia A. Barnes
Marcia A. Barnes
Affiliation:
University of Texas Health Science Center, Houston
Get access

Summary

Introduction

There have been remarkable advances in genetics over the past decade including the sequencing of the human genome which was completed in 2003, 50 years after the discovery of the double-helix structure of DNA by Watson and Crick (Valle, 2004). These advances have furthered our understanding of many forms of mental retardation, including X-linked mental retardation of which fragile X syndrome (FXS) is the most common type.

There are approximately 30, 000 genes in the human genome, and approximately 1000 genes on the X chromosome. Over 200 of these genes on the X chromosome have been associated with mental retardation. The X chromosome has more genes associated with mental retardation than any other chromosome. Approximately 20–25% of all cases of mental retardation are X-linked. Because males only have one X chromosome, they are much more vulnerable to the effects of an abnormal gene on the chromosome. There are approximately 20% more males with mental retardation than females in the general population. In this chapter we will review the most common inherited cause of mental retardation and neurodegeneration; fragile X associated tremor/ataxia syndrome (FXTAS), the most common cause of ataxia in those over 50 years of age; and the fragile X mental retardation 1 gene (FMR1), the most common gene associated with X-linked mental retardation.

Type
Chapter
Information
Genes, Brain and Development
The Neurocognition of Genetic Disorders
 , pp. 3 - 18
Publisher: Cambridge University Press
Print publication year: 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abbeduto, L., Brady, N., & Kover, S. T. (2007). Language development and fragile X syndrome: Profiles, syndrome-specificity, and within-syndrome differences. Mental Retardation and Developmental Disabilities Research Reviews, 13, 36–46.CrossRefGoogle ScholarPubMed
Abbeduto, L., Murphy, M. M., Kover, S. T., et al. (2008). Signaling noncomprehension of language: A comparison of fragile X syndrome and Down syndrome. American Journal on Mental Retardation, 113, 214–30.CrossRefGoogle ScholarPubMed
Allen, E. G., He, W., Yadav-Shah, M., & Sherman, S. L. (2004). A study of the distributional characteristics of FMR1 transcript levels in 238 individuals. Human Genetics, 114, 439–47.Google ScholarPubMed
Allingham-Hawkins, D. J., Babul-Hirji, R., Chitayat, D., 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. American Journal of Medical Genetics, 83, 322–5.3.0.CO;2-B>CrossRefGoogle ScholarPubMed
Arocena, D. G., Iwahashi, C. K., Won, N., et al. (2005). Induction of inclusion formation and disruption of lamin A/C structure by premutation CGG-repeat RNA in human cultured neural cells. Human Molecular Genetics, 14, 1–11.CrossRefGoogle ScholarPubMed
Aziz, M., Stathopulu, E., Callias, M., et al. (2003). Clinical features of boys with fragile X premutations and intermediate alleles. American Journal of Medical Genetics, 121B, 119–27.CrossRefGoogle Scholar
Bailey, D. B., Jr. (2004). Newborn screening for fragile X syndrome. Mental Retardation and Developmental Disabilities Research Reviews, 10, 3–10.CrossRefGoogle ScholarPubMed
Bailey, D. B., Jr., Hatton, D. D., Mesibov, G., Ament, N., & Skinner, M. (2000). Early development, temperament and functional impairment in autism and fragile X syndrome. Journal of Autism and Developmental Disorders, 30, 49–59.CrossRefGoogle ScholarPubMed
Bear, M. F., Huber, K. M., & Warren, S. T. (2004). The mGluR theory of fragile X mental retardation. Trends in Neuroscience, 27, 370–7.CrossRefGoogle ScholarPubMed
Bennetto, L., Pennington, B. F., & Rogers, S. J. (1996). Intact and impaired memory functions in autism. Child Development, 67, 1816–35.CrossRefGoogle ScholarPubMed
Berry-Kravis, E., Hessl, D., Coffey, S., et al. (2009). A pilot open label, single dose trial of fenobam in adults with fragile X syndrome. Journal of Medical Genetics, 46, 266–71.CrossRefGoogle ScholarPubMed
Berry-Kravis, E., Sumis, A., Hervey, C., et al. (2008). Open-label treatment trial of lithium to target the underlying defect in fragile X syndrome. Journal of Developmental and Behavioral Pediatrics, 29, 293–302.CrossRefGoogle ScholarPubMed
Brunberg, J. A., Jacquemont, S., Hagerman, R. J., et al. (2002). Fragile X premutation carriers: Characteristic MR imaging findings in adult males with progressive cerebellar and cognitive dysfunction. American Journal of Neuroradiology, 23, 1757–66.Google ScholarPubMed
Coffey, S. M., Cook, K., Tartaglia, N., et al. (2008). Expanded clinical phenotype of women with the FMR1 premutation. American Journal of Medical Genetics, 146A, 1009–16.CrossRefGoogle Scholar
Cohen, I. L. (1995). Behavioral profiles of autistic and non autistic fragile X males. Developmental Brain Dysfunction, 8, 252–69.Google Scholar
Cornish, K. M., Kogan, C., Turk, J., et al. (2005). The emerging fragile X premutation phenotype: Evidence from the domain of social cognition. Brain and Cognition, 57, 53–60.CrossRefGoogle ScholarPubMed
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, 269–74.CrossRefGoogle ScholarPubMed
Demark, J. L., Feldman, M. A., & Holden, J. J. (2003). Behavioral relationship between autism and fragile X syndrome. American Journal on Mental Retardation, 108, 314–26.2.0.CO;2>CrossRefGoogle ScholarPubMed
Derogatis, L. R. (1994). Symptom Checklist-90-R (SCL-90-R): Administration, Scoring, and Procedures Manual. Minneapolis: National Computer Systems.Google Scholar
Dombrowski, C., Levesque, S., 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, 371–8.CrossRefGoogle ScholarPubMed
Dorn, M. B., Mazzocco, M. M., & Hagerman, R. J. (1994). Behavioral and psychiatric disorders in adult male carriers of fragile X. Journal of American Academy of Child and Adolescent Psychiatry, 33, 256–64.CrossRefGoogle ScholarPubMed
Farzin, F., Perry, H., Hessl, D., 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, S137–44.CrossRefGoogle ScholarPubMed
Franke, P., Leboyer, M., Hardt, J., et al. (1999). Neuropsychological profiles of FMR-1 premutation and full-mutation carrier females. Psychiatry Research, 87, 223–31.CrossRefGoogle ScholarPubMed
Goodlin-Jones, B., Tassone, F., Gane, L. W., & Hagerman, R. J. (2004). Autistic spectrum disorder and the fragile X premutation. Journal of Developmental Behavioral Pediatrics, 25, 392–8.CrossRefGoogle ScholarPubMed
Greco, C. M., Berman, R. F., Martin, R. M., et al. (2006). Neuropathology of fragile X-associated tremor/ataxia syndrome (FXTAS). Brain, 129(Pt. 1), 243–55.CrossRefGoogle Scholar
Greco, C. M., Hagerman, R. J., Tassone, F., et al. (2002). Neuronal intranuclear inclusions in a new cerebellar tremor/ataxia syndrome among fragile X carriers. Brain, 125, 1760–71.CrossRefGoogle Scholar
Hagerman, P. J. (2008). The fragile X prevalence paradox. Journal of Medical Genetics, 45, 498–9.CrossRefGoogle ScholarPubMed
Hagerman, R. J. (2002a). Physical and behavioral phenotype. In Hagerman, R. J. & Hagerman, P. J. (Eds.), Fragile X Syndrome: Diagnosis, Treatment and Research, 3rd edn. (pp. 3–109). Baltimore: The Johns Hopkins University Press.Google Scholar
Hagerman, R. J. (2002b). Medical follow-up and pharmacotherapy. In Hagerman, R. J. & Hagerman, P. J. (Eds.), Fragile X Syndrome: Diagnosis, Treatment and Research, 3rd edn.(pp. 287–338). Baltimore: The Johns Hopkins University Press.Google Scholar
Hagerman, R. J. (2006). Lessons from fragile X regarding neurobiology, autism, and neurodegeneration. Journal of Developmental and Behavioral Pediatrics, 27, 63–74.CrossRefGoogle ScholarPubMed
Hagerman, R. J. & Hagerman, P. J. (2002a). The fragile X premutation: Into the phenotypic fold. Current Opinion in Genetics and Development, 12, 278–83.CrossRefGoogle ScholarPubMed
Hagerman, R. J. & Hagerman, P. J. (2002b). Fragile X Syndrome: Diagnosis, Treatment, and Research, 3rd edn. Baltimore: The Johns Hopkins University Press.CrossRefGoogle Scholar
Hagerman, P. J. & Hagerman, R. J. (2004a). The fragile-X premutation: A maturing perspective. American Journal of Human Genetics, 74, 805–16.CrossRefGoogle ScholarPubMed
Hagerman, P. J. & Hagerman, R. J. (2004b). Fragile X-associated tremor/ataxia syndrome (FXTAS). Mental Retardation and Developmental Disabilities Research Reviews, 10, 25–30.CrossRefGoogle Scholar
Hagerman, R. J., Berry-Kravis, E., Kaufmann, W. E., et al. (2009). Advances in the treatment of fragile X syndrome. Pediatrics, 123, 378–90.CrossRefGoogle ScholarPubMed
Hagerman, R. J., Hall, D. A., Coffey, S., et al. (2008). Treatment of fragile X-associated tremor ataxia syndrome (FXTAS) and related neurological problems. Clinical Interventions in Aging, 3, 251–62.CrossRefGoogle ScholarPubMed
Hagerman, R. J., Leavitt, B. R., Farzin, F., et al. (2004). Fragile-X-associated tremor/ataxia syndrome (FXTAS) in females with the FMR1 premutation. American Journal of Human Genetics, 74, 1051–6.CrossRefGoogle ScholarPubMed
Hagerman, R. J., Ono, M. Y., & Hagerman, P. J. (2005). Recent advances in fragile X: A model for autism and neurodegeneration. Current Opinion in Psychiatry, 18, 490–6.CrossRefGoogle ScholarPubMed
Hagerman, R. J., Staley, L. W., O'Conner, R., et al. (1996). Learning-disabled males with a fragile X CGG expansion in the upper premutation size range. Pediatrics, 97, 122–6.Google ScholarPubMed
Hatton, D., Hooper, S. R., Bailey, D. B., Skinner, M. L., Sullivan, K. M., & Wheeler, A. (2002). Problem behavior in boys with fragile X syndrome. American Journal of Medical Genetics, 108, 105–16.CrossRefGoogle ScholarPubMed
Hatton, D. D., Sideris, J., Skinner, M., et al. (2006). Autistic behavior in children with fragile X syndrome: Prevalence, stability, and the impact of FMRP. American Journal of Medical Genetics A, 140, 1804–13.CrossRefGoogle Scholar
Hatton, D. D., Wheeler, A. C., Skinner, M. L., et al. (2003). Adaptive behavior in children with fragile X syndrome. American Journal on Mental Retardation, 108, 373–90.2.0.CO;2>CrossRefGoogle ScholarPubMed
Hessl, D., Tassone, F., Loesch, D. Z., 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 B Neuropsychiatric Genetics, 139, 115–21.CrossRefGoogle Scholar
Hinds, H. L., Ashley, C. T., Sutcliffe, J. S., et al. (1993). Tissue specific expression of FMR-1 provides evidence for a functional role in fragile X syndrome. Nature Genetics, 3, 36–43 [published erratum appears in Nature Genetics, 5, 312].CrossRefGoogle ScholarPubMed
Huber, K. M., Gallagher, S. M., Warren, S. T., & Bear, M. F. (2002). Altered synaptic plasticity in a mouse model of fragile X mental retardation. Proceedings of the National Academy of Sciences of the United States of America, 99, 7746–50.CrossRefGoogle Scholar
Hull, C. & Hagerman, R. J. (1993). A study of the physical, behavioral, and medical phenotype, including anthropometric measures, of females with fragile X syndrome. American Journal of Diseases of Children, 147, 1236–41.Google ScholarPubMed
Iwahashi, C. K., Yasui, D. H., An, H. J., et al. (2006). Protein composition of the intranuclear inclusions of FXTAS. Brain. 129, 256–71.CrossRefGoogle ScholarPubMed
Jacquemont, S., Hagerman, R. J., Leehey, M. A., et al. (2003a). Penetrance of the fragile X-associated tremor/ataxia syndrome (FXTAS) in a premutation carrier population: Initial results from a California family-based study. American Journal of Human Genetics, 53rd Annual Meeting, Los Angeles, CA., 73(Suppl), A10:163.Google Scholar
Jacquemont, S., Hagerman, R. J., Leehey, M., et al. (2003b). Fragile X premutation tremor/ataxia syndrome: Molecular, clinical, and neuroimaging correlates. American Journal of Human Genetics, 72, 869–78.CrossRefGoogle ScholarPubMed
Jacquemont, S., Hagerman, R. J., Leehey, M. A., et al. (2004). Penetrance of the fragile X-associated tremor/ataxia syndrome in a premutation carrier population. Journal of the American Medical Association, 291, 460–9.CrossRefGoogle Scholar
Jacquemont, S., Leehey, M. A., Hagerman, R. J., Beckett, L. A., & Hagerman, P. J. (2006). Size bias of fragile X premutation alleles in late-onset movement disorders. Journal of Medical Genetics, 43, 804–9.CrossRefGoogle ScholarPubMed
Jakala, P., Hanninen, T., Ryynanen, M., et al. (1997). Fragile-X: Neuropsychological test performance, CGG triplet repeat lengths, and hippocampal volumes. Journal of Clinical Investigation, 100, 331–8.CrossRefGoogle ScholarPubMed
Johnston, C., Eliez, S., Dyer-Friedman, J., et al. (2001). Neurobehavioral phenotype in carriers of the fragile X premutation. American Journal of Medical Genetics, 103, 314–9.CrossRefGoogle ScholarPubMed
Kau, A. S., Tierney, E., Bukelis, I., et al. (2004). Social behavior profile in young males with fragile X syndrome: Characteristics and specificity. American Journal of Medical Genetics, 126A, 9–17.CrossRefGoogle Scholar
Kaufmann, W. E., Cortell, R., Kau, A. S., et al. (2004). Autism spectrum disorder in fragile X syndrome: Communication, social interaction, and specific behaviors. American Journal of Medical Genetics, 129A, 225–34.CrossRefGoogle Scholar
Kenneson, A., Zhang, F., Hagedorn, C. H., & Warren, S. T. (2001). Reduced FMRP and increased FMR1 transcription is proportionally associated with CGG repeat number in intermediate-length and premutation carriers. Human Molecular Genetics, 10, 1449–54.CrossRefGoogle ScholarPubMed
Koldewyn, K., Hessl, D., Adams, J., et al. (2008). Reduced hippocampal activation during recall is associated with elevated FMR1 mRNA and psychiatric symptoms in men with the fragile X premutation. Brain Imaging and Behavior, 2, 105–16.CrossRefGoogle ScholarPubMed
Loesch, D. Z., Huggins, R. M., & Hagerman, R. J. (2004). Phenotypic variation and FMRP levels in fragile X. Mental Retardation and Developmental Disabilities Research Reviews, 10, 31–41.CrossRefGoogle ScholarPubMed
Loesch, D. Z., Litewka, L., Brotchie, P., Huggins, R. M., Tassone, F., & Cook, M. (2005). Magnetic resonance imaging study in older fragile X premutation male carriers. Annals of Neurology, 58, 326–30.CrossRefGoogle ScholarPubMed
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 Disorders, 27, 415–35.CrossRefGoogle ScholarPubMed
McConkie-Rosell, A., Finucane, B., Cronister, A., Abrams, L., Bennett, R. L., & Pettersen, B. J. (2005). Genetic counseling for fragile X syndrome: Updated recommendations of the National Society of Genetic Counselors. Journal of Genetic Counseling, 14, 249–70.CrossRefGoogle ScholarPubMed
Moore, C. J., Daly, E. M., Schmitz, N., et al. (2004a). A neuropsychological investigation of male premutation carriers of fragile X syndrome. Neuropsychologia, 42, 1934–47.CrossRefGoogle ScholarPubMed
Moore, C. J., Daly, E. M., Tassone, F., et al. (2004b). The effect of pre-mutation of X chromosome CGG trinucleotide repeats on brain anatomy. Brain, 127, 2672–81.CrossRefGoogle ScholarPubMed
Murphy, D. G., Mentis, M. J., Pietrini, P., et al. (1999). Premutation female carriers of fragile X syndrome: A pilot study on brain anatomy and metabolism. Journal of American Academy of Child and Adolescent Psychiatry, 38, 1294–301.CrossRefGoogle ScholarPubMed
Murray, A., Ennis, S., MacSwiney, F., Webb, J., & Morton, N. E. (2000). Reproductive and menstrual history of females with fragile X expansions. European Journal of Human Genetics, 8, 247–52.CrossRefGoogle ScholarPubMed
Philofsky, A., Hepburn, S. L., Hayes, A., Hagerman, R., & Rogers, S. J. (2004). Linguistic and cognitive functioning and autism symptoms in young children with fragile X syndrome. American Journal of Mental Retardation, 109, 208–18.2.0.CO;2>CrossRefGoogle ScholarPubMed
Reiss, A. L., Freund, L., Abrams, M. T., Boehm, C., & Kazazian, H. (1993). Neurobehavioral effects of the fragile X premutation in adult women: A controlled study. American Journal of Human Genetics, 52, 884–94.Google ScholarPubMed
Riddle, J. E., Cheema, A., Sobesky, W. E., et al. (1998). Phenotypic involvement in females with the FMR1 gene mutation. American Journal on Mental Retardation, 102, 590–601.2.0.CO;2>CrossRefGoogle ScholarPubMed
Roberts, J. E., Bailey, D. B., Jr., Mankowski, J., et al. (2009). Mood and anxiety disorders in females with the FMR1 premutation. American Journal of Medical Genetics Neuropsychiatric Genetics, 150B, 130–9.CrossRefGoogle Scholar
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 Behavioral Pediatrics, 22, 409–17.CrossRefGoogle ScholarPubMed
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, 1006–18.Google ScholarPubMed
Schwartz, C. E., Dean, J., Howard-Peebles, P. N., et al. (1994). Obstetrical and gynecological complications in fragile X carriers: A multicenter study. American Journal of Medical Genetics, 51, 400–2.CrossRefGoogle ScholarPubMed
Sherman, S. L. (2000). Premature ovarian failure in the fragile X syndrome. American Journal of Medical Genetics, 97, 189–94.3.0.CO;2-J>CrossRefGoogle ScholarPubMed
Sherman, S., Pletcher, B. A., & Driscoll, D. A. (2005). Fragile X syndrome: Diagnostic and carrier testing. Genetics in Medicine, 7, 584–7.CrossRefGoogle ScholarPubMed
Sobesky, W. E., Pennington, B. F., Porter, D., Hull, C. E., & Hagerman, R. J. (1994). Emotional and neurocognitive deficits in fragile X. American Journal of Medical Genetics, 51, 378–85.CrossRefGoogle ScholarPubMed
Sobesky, W. E., Taylor, A. K., Pennington, B. F., Bennetto, L., Porter, D., & Hagerman, R. J. (1996). Molecular-clinical correlations in females with fragile X. American Journal of Medical Genetics, 64, 340–5.3.0.CO;2-E>CrossRefGoogle ScholarPubMed
Sullivan, A. K., Marcus, M., Epstein, M. P., et al. (2005). Association of FMR1 repeat size with ovarian dysfunction. Human Reproduction, 20, 402–12.CrossRefGoogle ScholarPubMed
Tassone, F., Greco, C., Berman, R. F., et al. (2005). Clinical and Molecular Correlations in FXTAS. Paper presented at 55th Annual Meeting of the American Society of Human Genetics, October 25–29. Salt Lake City, UT.Google Scholar
Tassone, F., Hagerman, R. J., Chamberlain, W. D., & Hagerman, P. J. (2000a). Transcription of the FMR1 gene in individuals with fragile X syndrome. American Journal of Medical Genetics, 97, 195–203.3.0.CO;2-R>CrossRefGoogle ScholarPubMed
Tassone, F., Hagerman, R. J., Loesch, D. Z., Lachiewicz, A., Taylor, A. K., & Hagerman, P. J. (2000b). Fragile X males with unmethylated, full mutation trinucleotide repeat expansions have elevated levels of FMR1 messenger RNA. American Journal of Medical Genetics, 94, 232–6.3.0.CO;2-H>CrossRefGoogle ScholarPubMed
Tassone, F., Hagerman, R. J., Taylor, A. K., Gane, L. W., Godfrey, T. E., & Hagerman, P. J. (2000c). Elevated levels of FMR1 mRNA in carrier males: A new mechanism of involvement in fragile X syndrome. American Journal of Human Genetics, 66, 6–15.CrossRefGoogle ScholarPubMed
Tassone, F., Hagerman, R. J., Taylor, A. K., et al. (2000d). Clinical involvement and protein expression in individuals with the FMR1 premutation. American Journal of Medical Genetics, 91, 144–52.3.0.CO;2-V>CrossRefGoogle ScholarPubMed
Tassone, F., Iwahashi, C., & Hagerman, P. J. (2004). FMR1 RNA within the intranuclear inclusions of fragile X-associated tremor/ataxia syndrome (FXTAS). RNA Biology, 1, 103–5.CrossRefGoogle Scholar
Tassone, F., Longshore, J., Zunich, J., Steinbach, P., Salat, U., & Taylor, A. K. (1999). Tissue-specific methylation differences in a fragile X premutation carrier. Clinical Genetics, 55, 346–51.CrossRefGoogle Scholar
Turk, J. & Graham, P. (1997). Fragile X syndrome, autism, and autistic features. Autism, 1, 175–97.CrossRefGoogle Scholar
Valle, D. (2004). Genetics, individuality, and medicine in the 21st century. American Journal of Human Genetics, 74, 374–81.CrossRefGoogle ScholarPubMed
Vianna-Morgante, A. M. & Costa, S. S. (2000). Premature ovarian failure is associated with maternally and paternally inherited premutation in Brazilian families with fragile X [see comments] [letter]. American Journal of Human Genetics, 67, 254–5; discussion 256–8.CrossRefGoogle Scholar
Welt, C. K., Smith, P. C., & Taylor, A. E. (2004). Evidence of early ovarian aging in fragile X premutation carriers. Journal of Clinical Endocrinology Metabolism, 89, 4569–74.CrossRefGoogle ScholarPubMed
Wittenberger, M. D., Hagerman, R. J., Sherman, S. L., et al. (2007). The FMR1 premutation and reproduction. Fertility and Sterility, 87, 456–65.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×