Skip to main content
NCBI home page
The Western Journal of Medicine logoLink to The Western Journal of Medicine
. 1997 Feb;166(2):129–137.

Fragile X syndrome. Molecular and clinical insights and treatment issues.

R J Hagerman 1
PMCID: PMC1304031  PMID: 9109330

Abstract

The fragile X syndrome is the most common inherited cause of mental retardation that is known. The prevalence of mental retardation from this syndrome ranges from 1 in 1,250 to 1 in 4,000 in the general population, although the prevalence of female carriers has been reported to be as high as 1 in 259. The discovery of the FMR1 gene mutation in 1991 has simplified diagnosis, enhanced our understanding of the spectrum of involvement in the fragile X syndrome, and stimulated research regarding the normal function of the FMR1 protein in brain development. Advances have also occurred in the treatment of the fragile X syndrome, and psychopharmacologic and educational interventions are reviewed here.

Full text

PDF
129

Images in this article

130Figure 1.
on p.130

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abrams M. T., Reiss A. L., Freund L. S., Baumgardner T. L., Chase G. A., Denckla M. B. Molecular-neurobehavioral associations in females with the fragile X full mutation. Am J Med Genet. 1994 Jul 15;51(4):317–327. doi: 10.1002/ajmg.1320510407. [DOI] [PubMed] [Google Scholar]
  2. Allingham-Hawkins D. J., Brown C. A., Babul R., Chitayat D., Krekewich K., Humphries T., Ray P. N., Teshima I. E. Tissue-specific methylation differences and cognitive function in fragile X premutation females. Am J Med Genet. 1996 Aug 9;64(2):329–333. doi: 10.1002/(SICI)1096-8628(19960809)64:2<329::AID-AJMG19>3.0.CO;2-H. [DOI] [PubMed] [Google Scholar]
  3. Arinami T., Sato M., Nakajima S., Kondo I. Auditory brain-stem responses in the fragile X syndrome. Am J Hum Genet. 1988 Jul;43(1):46–51. [PMC free article] [PubMed] [Google Scholar]
  4. Ashley C. T., Jr, Wilkinson K. D., Reines D., Warren S. T. FMR1 protein: conserved RNP family domains and selective RNA binding. Science. 1993 Oct 22;262(5133):563–566. doi: 10.1126/science.7692601. [DOI] [PubMed] [Google Scholar]
  5. Berry-Kravis E., Huttenlocher P. R. Cyclic AMP metabolism in fragile X syndrome. Ann Neurol. 1992 Jan;31(1):22–26. doi: 10.1002/ana.410310105. [DOI] [PubMed] [Google Scholar]
  6. Berry-Kravis E., Sklena P. Demonstration of abnormal cyclic AMP production in platelets from patients with fragile X syndrome. Am J Med Genet. 1993 Jan 1;45(1):81–87. doi: 10.1002/ajmg.1320450120. [DOI] [PubMed] [Google Scholar]
  7. Black S. H. Preimplantation genetic diagnosis. Curr Opin Pediatr. 1994 Dec;6(6):712–716. doi: 10.1097/00008480-199412000-00018. [DOI] [PubMed] [Google Scholar]
  8. Borghgraef M., Umans S., Steyaert J., Legius E., Fryns J. P. New findings in the behavioral profile of young FraX females. Am J Med Genet. 1996 Aug 9;64(2):346–349. doi: 10.1002/(SICI)1096-8628(19960809)64:2<346::AID-AJMG22>3.0.CO;2-E. [DOI] [PubMed] [Google Scholar]
  9. Brown W. T., Houck G. E., Jr, Jeziorowska A., Levinson F. N., Ding X., Dobkin C., Zhong N., Henderson J., Brooks S. S., Jenkins E. C. Rapid fragile X carrier screening and prenatal diagnosis using a nonradioactive PCR test. JAMA. 1993 Oct 6;270(13):1569–1575. [PubMed] [Google Scholar]
  10. Brown W. T. The FRAXE Syndrome: is it time for routine screening? Am J Hum Genet. 1996 May;58(5):903–905. [PMC free article] [PubMed] [Google Scholar]
  11. Butler M. G., Brunschwig A., Miller L. K., Hagerman R. J. Standards for selected anthropometric measurements in males with the fragile X syndrome. Pediatrics. 1992 Jun;89(6 Pt 1):1059–1062. [PMC free article] [PubMed] [Google Scholar]
  12. Butler M. G., Najjar J. L. Do some patients with fragile X syndrome have precocious puberty? Am J Med Genet. 1988 Dec;31(4):779–781. doi: 10.1002/ajmg.1320310408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Crabbe L. S., Bensky A. S., Hornstein L., Schwartz D. C. Cardiovascular abnormalities in children with fragile X syndrome. Pediatrics. 1993 Apr;91(4):714–715. [PubMed] [Google Scholar]
  14. De Boulle K., Verkerk A. J., Reyniers E., Vits L., Hendrickx J., Van Roy B., Van den Bos F., de Graaff E., Oostra B. A., Willems P. J. A point mutation in the FMR-1 gene associated with fragile X mental retardation. Nat Genet. 1993 Jan;3(1):31–35. doi: 10.1038/ng0193-31. [DOI] [PubMed] [Google Scholar]
  15. Ferri R., Musumeci S. A., Elia M., Del Gracco S., Scuderi C., Bergonzi P. BIT-mapped somatosensory evoked potentials in the fragile X syndrome. Neurophysiol Clin. 1994 Dec;24(6):413–426. doi: 10.1016/s0987-7053(05)80074-7. [DOI] [PubMed] [Google Scholar]
  16. Franke P., Maier W., Hautzinger M., Weiffenbach O., Gänsicke M., Iwers B., Poustka F., Schwab S. G., Froster U. Fragile-X carrier females: evidence for a distinct psychopathological phenotype? Am J Med Genet. 1996 Aug 9;64(2):334–339. doi: 10.1002/(SICI)1096-8628(19960809)64:2<334::AID-AJMG20>3.0.CO;2-F. [DOI] [PubMed] [Google Scholar]
  17. Fras I., Major L. F. Clinical experience with risperidone. J Am Acad Child Adolesc Psychiatry. 1995 Jul;34(7):833–833. doi: 10.1097/00004583-199507000-00003. [DOI] [PubMed] [Google Scholar]
  18. Freund L. S., Reiss A. L., Abrams M. T. Psychiatric disorders associated with fragile X in the young female. Pediatrics. 1993 Feb;91(2):321–329. [PubMed] [Google Scholar]
  19. Fryns J. P., Haspeslagh M., Dereymaeker A. M., Volcke P., Van den Berghe H. A peculiar subphenotype in the fra(X) syndrome: extreme obesity-short stature-stubby hands and feet-diffuse hyperpigmentation. Further evidence of disturbed hypothalamic function in the fra(X) syndrome? Clin Genet. 1987 Dec;32(6):388–392. doi: 10.1111/j.1399-0004.1987.tb03155.x. [DOI] [PubMed] [Google Scholar]
  20. Fu Y. H., Kuhl D. P., Pizzuti A., Pieretti M., Sutcliffe J. S., Richards S., Verkerk A. J., Holden J. J., Fenwick R. G., Jr, Warren S. T. Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell. 1991 Dec 20;67(6):1047–1058. doi: 10.1016/0092-8674(91)90283-5. [DOI] [PubMed] [Google Scholar]
  21. Gecz J., Gedeon A. K., Sutherland G. R., Mulley J. C. Identification of the gene FMR2, associated with FRAXE mental retardation. Nat Genet. 1996 May;13(1):105–108. doi: 10.1038/ng0596-105. [DOI] [PubMed] [Google Scholar]
  22. Gedeon A. K., Baker E., Robinson H., Partington M. W., Gross B., Manca A., Korn B., Poustka A., Yu S., Sutherland G. R. Fragile X syndrome without CCG amplification has an FMR1 deletion. Nat Genet. 1992 Aug;1(5):341–344. doi: 10.1038/ng0892-341. [DOI] [PubMed] [Google Scholar]
  23. Gillberg C., Persson E., Wahlström J. The autism-fragile-X syndrome (AFRAX): a population-based study of ten boys. J Ment Defic Res. 1986 Mar;30(Pt 1):27–39. doi: 10.1111/j.1365-2788.1986.tb01295.x. [DOI] [PubMed] [Google Scholar]
  24. Goldson E., Hagerman R. J. Fragile X syndrome and failure to thrive. Am J Dis Child. 1993 Jun;147(6):605–607. doi: 10.1001/archpedi.1993.02160300011002. [DOI] [PubMed] [Google Scholar]
  25. Gu Y., Lugenbeel K. A., Vockley J. G., Grody W. W., Nelson D. L. A de novo deletion in FMR1 in a patient with developmental delay. Hum Mol Genet. 1994 Sep;3(9):1705–1706. doi: 10.1093/hmg/3.9.1705. [DOI] [PubMed] [Google Scholar]
  26. Gu Y., Shen Y., Gibbs R. A., Nelson D. L. Identification of FMR2, a novel gene associated with the FRAXE CCG repeat and CpG island. Nat Genet. 1996 May;13(1):109–113. doi: 10.1038/ng0596-109. [DOI] [PubMed] [Google Scholar]
  27. Hagerman R. J., Altshul-Stark D., McBogg P. Recurrent otitis media in the fragile X syndrome. Am J Dis Child. 1987 Feb;141(2):184–187. doi: 10.1001/archpedi.1987.04460020074031. [DOI] [PubMed] [Google Scholar]
  28. Hagerman R. J., Amiri K., Cronister A. Fragile X checklist. Am J Med Genet. 1991 Feb-Mar;38(2-3):283–287. doi: 10.1002/ajmg.1320380223. [DOI] [PubMed] [Google Scholar]
  29. Hagerman R. J., Chudley A. E., Knoll J. H., Jackson A. W., 3rd, Kemper M., Ahmad R. Autism in fragile X females. Am J Med Genet. 1986 Jan-Feb;23(1-2):375–380. doi: 10.1002/ajmg.1320230129. [DOI] [PubMed] [Google Scholar]
  30. Hagerman R. J. Fragile X syndrome. Curr Probl Pediatr. 1987 Nov;17(11):621–674. doi: 10.1016/0045-9380(87)90011-9. [DOI] [PubMed] [Google Scholar]
  31. Hagerman R. J., Hull C. E., Safanda J. F., Carpenter I., Staley L. W., O'Connor R. A., Seydel C., Mazzocco M. M., Snow K., Thibodeau S. N. High functioning fragile X males: demonstration of an unmethylated fully expanded FMR-1 mutation associated with protein expression. Am J Med Genet. 1994 Jul 15;51(4):298–308. doi: 10.1002/ajmg.1320510404. [DOI] [PubMed] [Google Scholar]
  32. Hagerman R. J., Jackson C., Amiri K., Silverman A. C., O'Connor R., Sobesky W. Girls with fragile X syndrome: physical and neurocognitive status and outcome. Pediatrics. 1992 Mar;89(3):395–400. [PubMed] [Google Scholar]
  33. Hagerman R. J., Murphy M. A., Wittenberger M. D. A controlled trial of stimulant medication in children with the fragile X syndrome. Am J Med Genet. 1988 May-Jun;30(1-2):377–392. doi: 10.1002/ajmg.1320300138. [DOI] [PubMed] [Google Scholar]
  34. Hinton V. J., Brown W. T., Wisniewski K., Rudelli R. D. Analysis of neocortex in three males with the fragile X syndrome. Am J Med Genet. 1991 Dec 1;41(3):289–294. doi: 10.1002/ajmg.1320410306. [DOI] [PubMed] [Google Scholar]
  35. Hirst M., Grewal P., Flannery A., Slatter R., Maher E., Barton D., Fryns J. P., Davies K. Two new cases of FMR1 deletion associated with mental impairment. Am J Hum Genet. 1995 Jan;56(1):67–74. [PMC free article] [PubMed] [Google Scholar]
  36. Hodapp R. M., Dykens E. M., Hagerman R. J., Schreiner R., Lachiewicz A. M., Leckman J. F. Developmental implications of changing trajectories of IQ in males with fragile X syndrome. J Am Acad Child Adolesc Psychiatry. 1990 Mar;29(2):214–219. doi: 10.1097/00004583-199003000-00009. [DOI] [PubMed] [Google Scholar]
  37. Hull C., Hagerman R. J. A study of the physical, behavioral, and medical phenotype, including anthropometric measures, of females with fragile X syndrome. Am J Dis Child. 1993 Nov;147(11):1236–1241. doi: 10.1001/archpedi.1993.02160350110017. [DOI] [PubMed] [Google Scholar]
  38. Khandjian E. W., Corbin F., Woerly S., Rousseau F. The fragile X mental retardation protein is associated with ribosomes. Nat Genet. 1996 Jan;12(1):91–93. doi: 10.1038/ng0196-91. [DOI] [PubMed] [Google Scholar]
  39. Knight S. J., Ritchie R. J., Chakrabarti L., Cross G., Taylor G. R., Mueller R. F., Hurst J., Paterson J., Yates J. R., Dow D. J. A study of FRAXE in mentally retarded individuals referred for fragile X syndrome (FRAXA) testing in the United Kingdom. Am J Hum Genet. 1996 May;58(5):906–913. [PMC free article] [PubMed] [Google Scholar]
  40. Lachiewicz A. M., Dawson D. V. Do young boys with fragile X syndrome have macroorchidism? Pediatrics. 1994 Jun;93(6 Pt 1):992–995. [PubMed] [Google Scholar]
  41. Lachiewicz A. M., Gullion C. M., Spiridigliozzi G. A., Aylsworth A. S. Declining IQs of young males with the fragile X syndrome. Am J Ment Retard. 1987 Nov;92(3):272–278. [PubMed] [Google Scholar]
  42. Lachiewicz A. M., Spiridigliozzi G. A., McConkie-Rosell A., Burgess D., Feng Y., Warren S. T., Tarleton J. A fragile X male with a broad smear on Southern blot analysis representing 100-500 CGG repeats and no methylation at the EagI site of the FMR-1 gene. Am J Med Genet. 1996 Aug 9;64(2):278–282. doi: 10.1002/(SICI)1096-8628(19960809)64:2<278::AID-AJMG9>3.0.CO;2-Q. [DOI] [PubMed] [Google Scholar]
  43. Loehr J. P., Synhorst D. P., Wolfe R. R., Hagerman R. J. Aortic root dilatation and mitral valve prolapse in the fragile X syndrome. Am J Med Genet. 1986 Jan-Feb;23(1-2):189–194. doi: 10.1002/ajmg.1320230113. [DOI] [PubMed] [Google Scholar]
  44. Loesch D. Z., Huggins R. M., Hoang N. H. Growth in stature in fragile X families: a mixed longitudinal study. Am J Med Genet. 1995 Sep 11;58(3):249–256. doi: 10.1002/ajmg.1320580311. [DOI] [PubMed] [Google Scholar]
  45. Loesch D. Z., Huggins R., Hay D. A., Gedeon A. K., Mulley J. C., Sutherland G. R. Genotype-phenotype relationships in fragile X syndrome: a family study. Am J Hum Genet. 1993 Nov;53(5):1064–1073. [PMC free article] [PubMed] [Google Scholar]
  46. Loesch D. Z., Huggins R., Petrovic V., Slater H. Expansion of the CGG repeat in fragile X in the FMR1 gene depends on the sex of the offspring. Am J Hum Genet. 1995 Dec;57(6):1408–1413. [PMC free article] [PubMed] [Google Scholar]
  47. Lugenbeel K. A., Peier A. M., Carson N. L., Chudley A. E., Nelson D. L. Intragenic loss of function mutations demonstrate the primary role of FMR1 in fragile X syndrome. Nat Genet. 1995 Aug;10(4):483–485. doi: 10.1038/ng0895-483. [DOI] [PubMed] [Google Scholar]
  48. Maino D. M., Schlange D., Maino J. H., Caden B. Ocular anomalies in fragile X syndrome. J Am Optom Assoc. 1990 Apr;61(4):316–323. [PubMed] [Google Scholar]
  49. Maino D. M., Wesson M., Schlange D., Cibis G., Maino J. H. Optometric findings in the fragile X syndrome. Optom Vis Sci. 1991 Aug;68(8):634–640. doi: 10.1097/00006324-199108000-00010. [DOI] [PubMed] [Google Scholar]
  50. Mazzocco M. M., Pennington B. F., Hagerman R. J. The neurocognitive phenotype of female carriers of fragile X: additional evidence for specificity. J Dev Behav Pediatr. 1993 Oct;14(5):328–335. [PubMed] [Google Scholar]
  51. McConkie-Rosell A., Lachiewicz A. M., Spiridigliozzi G. A., Tarleton J., Schoenwald S., Phelan M. C., Goonewardena P., Ding X., Brown W. T. Evidence that methylation of the FMR-I locus is responsible for variable phenotypic expression of the fragile X syndrome. Am J Hum Genet. 1993 Oct;53(4):800–809. [PMC free article] [PubMed] [Google Scholar]
  52. McConkie-Rosell A., Robinson H., Wake S., Staley L. W., Heller K., Cronister A. Dissemination of genetic risk information to relatives in the fragile X syndrome: guidelines for genetic counselors. Am J Med Genet. 1995 Dec 4;59(4):426–430. doi: 10.1002/ajmg.1320590406. [DOI] [PubMed] [Google Scholar]
  53. Meijer H., de Graaff E., Merckx D. M., Jongbloed R. J., de Die-Smulders C. E., Engelen J. J., Fryns J. P., Curfs P. M., Oostra B. A. A deletion of 1.6 kb proximal to the CGG repeat of the FMR1 gene causes the clinical phenotype of the fragile X syndrome. Hum Mol Genet. 1994 Apr;3(4):615–620. doi: 10.1093/hmg/3.4.615. [DOI] [PubMed] [Google Scholar]
  54. Merenstein S. A., Shyu V., Sobesky W. E., Staley L., Berry-Kravis E., Nelson D. L., Lugenbeel K. A., Taylor A. K., Pennington B. F., Hagerman R. J. Fragile X syndrome in a normal IQ male with learning and emotional problems. J Am Acad Child Adolesc Psychiatry. 1994 Nov-Dec;33(9):1316–1321. doi: 10.1097/00004583-199411000-00014. [DOI] [PubMed] [Google Scholar]
  55. Merenstein S. A., Sobesky W. E., Taylor A. K., Riddle J. E., Tran H. X., Hagerman R. J. Molecular-clinical correlations in males with an expanded FMR1 mutation. Am J Med Genet. 1996 Aug 9;64(2):388–394. doi: 10.1002/(SICI)1096-8628(19960809)64:2<388::AID-AJMG31>3.0.CO;2-9. [DOI] [PubMed] [Google Scholar]
  56. Moore P. S., Chudley A. E., Winter J. S. True precocious puberty in a girl with the fragile X syndrome. Am J Med Genet. 1990 Oct;37(2):265–267. doi: 10.1002/ajmg.1320370221. [DOI] [PubMed] [Google Scholar]
  57. O'Hare J. P., O'Brien I. A., Arendt J., Astley P., Ratcliffe W., Andrews H., Walters R., Corrall R. J. Does melatonin deficiency cause the enlarged genitalia of the fragile-X syndrome? Clin Endocrinol (Oxf) 1986 Mar;24(3):327–333. doi: 10.1111/j.1365-2265.1986.tb03274.x. [DOI] [PubMed] [Google Scholar]
  58. Oostra B. A., Willems P. J. A fragile gene. Bioessays. 1995 Nov;17(11):941–947. doi: 10.1002/bies.950171107. [DOI] [PubMed] [Google Scholar]
  59. Pieretti M., Zhang F. P., Fu Y. H., Warren S. T., Oostra B. A., Caskey C. T., Nelson D. L. Absence of expression of the FMR-1 gene in fragile X syndrome. Cell. 1991 Aug 23;66(4):817–822. doi: 10.1016/0092-8674(91)90125-i. [DOI] [PubMed] [Google Scholar]
  60. Quan F., Zonana J., Gunter K., Peterson K. L., Magenis R. E., Popovich B. W. An atypical case of fragile X syndrome caused by a deletion that includes the FMR1 gene. Am J Hum Genet. 1995 May;56(5):1042–1051. [PMC free article] [PubMed] [Google Scholar]
  61. Quintana H., Keshavan M. Case study: risperidone in children and adolescents with schizophrenia. J Am Acad Child Adolesc Psychiatry. 1995 Oct;34(10):1292–1296. doi: 10.1097/00004583-199510000-00014. [DOI] [PubMed] [Google Scholar]
  62. Reiss A. L., Abrams M. T., Greenlaw R., Freund L., Denckla M. B. Neurodevelopmental effects of the FMR-1 full mutation in humans. Nat Med. 1995 Feb;1(2):159–167. doi: 10.1038/nm0295-159. [DOI] [PubMed] [Google Scholar]
  63. Reiss A. L., Aylward E., Freund L. S., Joshi P. K., Bryan R. N. Neuroanatomy of fragile X syndrome: the posterior fossa. Ann Neurol. 1991 Jan;29(1):26–32. doi: 10.1002/ana.410290107. [DOI] [PubMed] [Google Scholar]
  64. Reiss A. L., Freund L., Abrams M. T., Boehm C., Kazazian H. Neurobehavioral effects of the fragile X premutation in adult women: a controlled study. Am J Hum Genet. 1993 May;52(5):884–894. [PMC free article] [PubMed] [Google Scholar]
  65. Reiss A. L., Freund L., Tseng J. E., Joshi P. K. Neuroanatomy in fragile X females: the posterior fossa. Am J Hum Genet. 1991 Aug;49(2):279–288. [PMC free article] [PubMed] [Google Scholar]
  66. Reiss A. L., Lee J., Freund L. Neuroanatomy of fragile X syndrome: the temporal lobe. Neurology. 1994 Jul;44(7):1317–1324. doi: 10.1212/wnl.44.7.1317. [DOI] [PubMed] [Google Scholar]
  67. Reiss A. L., Patel S., Kumar A. J., Freund L. Preliminary communication: neuroanatomical variations of the posterior fossa in men with the fragile X (Martin-Bell) syndrome. Am J Med Genet. 1988 Oct;31(2):407–414. doi: 10.1002/ajmg.1320310220. [DOI] [PubMed] [Google Scholar]
  68. Ritchie R. J., Knight S. J., Hirst M. C., Grewal P. K., Bobrow M., Cross G. S., Davies K. E. The cloning of FRAXF: trinucleotide repeat expansion and methylation at a third fragile site in distal Xqter. Hum Mol Genet. 1994 Dec;3(12):2115–2121. doi: 10.1093/hmg/3.12.2115. [DOI] [PubMed] [Google Scholar]
  69. Rousseau F., Heitz D., Tarleton J., MacPherson J., Malmgren H., Dahl N., Barnicoat A., Mathew C., Mornet E., Tejada I. A multicenter study on genotype-phenotype correlations in the fragile X syndrome, using direct diagnosis with probe StB12.3: the first 2,253 cases. Am J Hum Genet. 1994 Aug;55(2):225–237. [PMC free article] [PubMed] [Google Scholar]
  70. Rousseau F., Robb L. J., Rouillard P., Der Kaloustian V. M. No mental retardation in a man with 40% abnormal methylation at the FMR-1 locus and transmission of sperm cell mutations as premutations. Hum Mol Genet. 1994 Jun;3(6):927–930. doi: 10.1093/hmg/3.6.927. [DOI] [PubMed] [Google Scholar]
  71. Rousseau F., Rouillard P., Morel M. L., Khandjian E. W., Morgan K. Prevalence of carriers of premutation-size alleles of the FMRI gene--and implications for the population genetics of the fragile X syndrome. Am J Hum Genet. 1995 Nov;57(5):1006–1018. [PMC free article] [PubMed] [Google Scholar]
  72. Rudelli R. D., Brown W. T., Wisniewski K., Jenkins E. C., Laure-Kamionowska M., Connell F., Wisniewski H. M. Adult fragile X syndrome. Clinico-neuropathologic findings. Acta Neuropathol. 1985;67(3-4):289–295. doi: 10.1007/BF00687814. [DOI] [PubMed] [Google Scholar]
  73. Schapiro M. B., Murphy D. G., Hagerman R. J., Azari N. P., Alexander G. E., Miezejeski C. M., Hinton V. J., Horwitz B., Haxby J. V., Kumar A. Adult fragile X syndrome: neuropsychology, brain anatomy, and metabolism. Am J Med Genet. 1995 Dec 18;60(6):480–493. doi: 10.1002/ajmg.1320600603. [DOI] [PubMed] [Google Scholar]
  74. Siomi M. C., Siomi H., Sauer W. H., Srinivasan S., Nussbaum R. L., Dreyfuss G. FXR1, an autosomal homolog of the fragile X mental retardation gene. EMBO J. 1995 Jun 1;14(11):2401–2408. doi: 10.1002/j.1460-2075.1995.tb07237.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Siomi M. C., Zhang Y., Siomi H., Dreyfuss G. Specific sequences in the fragile X syndrome protein FMR1 and the FXR proteins mediate their binding to 60S ribosomal subunits and the interactions among them. Mol Cell Biol. 1996 Jul;16(7):3825–3832. doi: 10.1128/mcb.16.7.3825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Smeets H. J., Smits A. P., Verheij C. E., Theelen J. P., Willemsen R., van de Burgt I., Hoogeveen A. T., Oosterwijk J. C., Oostra B. A. Normal phenotype in two brothers with a full FMR1 mutation. Hum Mol Genet. 1995 Nov;4(11):2103–2108. doi: 10.1093/hmg/4.11.2103. [DOI] [PubMed] [Google Scholar]
  77. Sobesky W. E., Hull C. E., Hagerman R. J. Symptoms of schizotypal personality disorder in fragile X women. J Am Acad Child Adolesc Psychiatry. 1994 Feb;33(2):247–255. doi: 10.1097/00004583-199402000-00014. [DOI] [PubMed] [Google Scholar]
  78. Sobesky W. E., Taylor A. K., Pennington B. F., Bennetto L., Porter D., Riddle J., Hagerman R. J. Molecular/clinical correlations in females with fragile X. Am J Med Genet. 1996 Aug 9;64(2):340–345. doi: 10.1002/(SICI)1096-8628(19960809)64:2<340::AID-AJMG21>3.0.CO;2-E. [DOI] [PubMed] [Google Scholar]
  79. Sreeram N., Wren C., Bhate M., Robertson P., Hunter S. Cardiac abnormalities in the fragile X syndrome. Br Heart J. 1989 Mar;61(3):289–291. doi: 10.1136/hrt.61.3.289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. St Clair D. M., Blackwood D. H., Oliver C. J., Dickens P. P3 abnormality in fragile X syndrome. Biol Psychiatry. 1987 Mar;22(3):303–312. doi: 10.1016/0006-3223(87)90148-x. [DOI] [PubMed] [Google Scholar]
  81. Staley-Gane L., Flynn L., Neitzel K., Cronister A., Hagerman R. J. Expanding the role of the genetic counselor. Am J Med Genet. 1996 Aug 9;64(2):382–387. doi: 10.1002/(SICI)1096-8628(19960809)64:2<382::AID-AJMG30>3.0.CO;2-9. [DOI] [PubMed] [Google Scholar]
  82. Steyaert J., Borghgraef M., Legius E., Fryns J. P. Molecular-intelligence correlations in young fragile X males with a mild CGG repeat expansion in the FMR1 gene. Am J Med Genet. 1996 Aug 9;64(2):274–277. doi: 10.1002/(SICI)1096-8628(19960809)64:2<274::AID-AJMG8>3.0.CO;2-U. [DOI] [PubMed] [Google Scholar]
  83. Tarleton J., Richie R., Schwartz C., Rao K., Aylsworth A. S., Lachiewicz A. An extensive de novo deletion removing FMR1 in a patient with mental retardation and the fragile X syndrome phenotype. Hum Mol Genet. 1993 Nov;2(11):1973–1974. doi: 10.1093/hmg/2.11.1973. [DOI] [PubMed] [Google Scholar]
  84. Taylor A. K., Safanda J. F., Fall M. Z., Quince C., Lang K. A., Hull C. E., Carpenter I., Staley L. W., Hagerman R. J. Molecular predictors of cognitive involvement in female carriers of fragile X syndrome. JAMA. 1994 Feb 16;271(7):507–514. [PubMed] [Google Scholar]
  85. Thompson N. M., Gulley M. L., Rogeness G. A., Clayton R. J., Johnson C., Hazelton B., Cho C. G., Zellmer V. T. Neurobehavioral characteristics of CGG amplification status in fragile X females. Am J Med Genet. 1994 Dec 15;54(4):378–383. doi: 10.1002/ajmg.1320540418. [DOI] [PubMed] [Google Scholar]
  86. Vanden Borre R., Vermote R., Buttiëns M., Thiry P., Dierick G., Geutjens J., Sieben G., Heylen S. Risperidone as add-on therapy in behavioural disturbances in mental retardation: a double-blind placebo-controlled cross-over study. Acta Psychiatr Scand. 1993 Mar;87(3):167–171. doi: 10.1111/j.1600-0447.1993.tb03350.x. [DOI] [PubMed] [Google Scholar]
  87. Verheij C., Bakker C. E., de Graaff E., Keulemans J., Willemsen R., Verkerk A. J., Galjaard H., Reuser A. J., Hoogeveen A. T., Oostra B. A. Characterization and localization of the FMR-1 gene product associated with fragile X syndrome. Nature. 1993 Jun 24;363(6431):722–724. doi: 10.1038/363722a0. [DOI] [PubMed] [Google Scholar]
  88. Verkerk A. J., Pieretti M., Sutcliffe J. S., Fu Y. H., Kuhl D. P., Pizzuti A., Reiner O., Richards S., Victoria M. F., Zhang F. P. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell. 1991 May 31;65(5):905–914. doi: 10.1016/0092-8674(91)90397-h. [DOI] [PubMed] [Google Scholar]
  89. Waldstein G., Mierau G., Ahmad R., Thibodeau S. N., Hagerman R. J., Caldwell S. Fragile X syndrome: skin elastin abnormalities. Birth Defects Orig Artic Ser. 1987;23(1):103–114. [PubMed] [Google Scholar]
  90. Warren S. T., Ashley C. T., Jr Triplet repeat expansion mutations: the example of fragile X syndrome. Annu Rev Neurosci. 1995;18:77–99. doi: 10.1146/annurev.ne.18.030195.000453. [DOI] [PubMed] [Google Scholar]
  91. Wisniewski K. E., Segan S. M., Miezejeski C. M., Sersen E. A., Rudelli R. D. The Fra(X) syndrome: neurological, electrophysiological, and neuropathological abnormalities. Am J Med Genet. 1991 Feb-Mar;38(2-3):476–480. doi: 10.1002/ajmg.1320380267. [DOI] [PubMed] [Google Scholar]
  92. Wright-Talamante C., Cheema A., Riddle J. E., Luckey D. W., Taylor A. K., Hagerman R. J. A controlled study of longitudinal IQ changes in females and males with fragile X syndrome. Am J Med Genet. 1996 Aug 9;64(2):350–355. doi: 10.1002/(SICI)1096-8628(19960809)64:2<350::AID-AJMG23>3.0.CO;2-D. [DOI] [PubMed] [Google Scholar]
  93. Zhang Y., O'Connor J. P., Siomi M. C., Srinivasan S., Dutra A., Nussbaum R. L., Dreyfuss G. The fragile X mental retardation syndrome protein interacts with novel homologs FXR1 and FXR2. EMBO J. 1995 Nov 1;14(21):5358–5366. doi: 10.1002/j.1460-2075.1995.tb00220.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  94. de Vries B. B., Robinson H., Stolte-Dijkstra I., Tjon Pian Gi C. V., Dijkstra P. F., van Doorn J., Halley D. J., Oostra B. A., Turner G., Niermeijer M. F. General overgrowth in the fragile X syndrome: variability in the phenotypic expression of the FMR1 gene mutation. J Med Genet. 1995 Oct;32(10):764–769. doi: 10.1136/jmg.32.10.764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  95. de Vries B. B., Wiegers A. M., Smits A. P., Mohkamsing S., Duivenvoorden H. J., Fryns J. P., Curfs L. M., Halley D. J., Oostra B. A., van den Ouweland A. M. Mental status of females with an FMR1 gene full mutation. Am J Hum Genet. 1996 May;58(5):1025–1032. [PMC free article] [PubMed] [Google Scholar]

Articles from Western Journal of Medicine are provided here courtesy of BMJ Publishing Group

RESOURCES