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J Med Genet. 1998 August; 35(8): 637–640.
PMCID: PMC1051387

Studies of FRAXA and FRAXE in women with premature ovarian failure.


Recent reports suggest that women with FRAXA premutations have an increased likelihood of having premature ovarian failure (POF). We screened 147 women with idiopathic POF for the number of trinucleotide repeats at the FRAXA and FRAXE loci. We found six women with FRAXA premutations, including four familial and two sporadic cases, but no women with FRAXA full mutations. At the FRAXE locus there were no pre- or full mutations but there was an excess of small alleles with fewer than 11 repeats, including at least one small deletion at or near the triplet. The association of FRAXA premutations with POF confirms that premutation alleles can affect ovarian development or function or both.

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Selected References

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  • McKinlay S, Jefferys M, Thompson B. An investigation of the age at menopause. J Biosoc Sci. 1972 Apr;4(2):161–173. [PubMed]
  • Coulam CB, Adamson SC, Annegers JF. Incidence of premature ovarian failure. Obstet Gynecol. 1986 Apr;67(4):604–606. [PubMed]
  • Powell CM, Taggart RT, Drumheller TC, Wangsa D, Qian C, Nelson LM, White BJ. Molecular and cytogenetic studies of an X;autosome translocation in a patient with premature ovarian failure and review of the literature. Am J Med Genet. 1994 Aug 1;52(1):19–26. [PubMed]
  • Aittomäki K, Lucena JL, Pakarinen P, Sistonen P, Tapanainen J, Gromoll J, Kaskikari R, Sankila EM, Lehväslaiho H, Engel AR, et al. Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell. 1995 Sep 22;82(6):959–968. [PubMed]
  • Page DC, Disteche CM, Simpson EM, de la Chapelle A, Andersson M, Alitalo T, Brown LG, Green P, Akots G. Chromosomal localization of ZFX--a human gene that escapes X inactivation--and its murine homologs. Genomics. 1990 May;7(1):37–46. [PubMed]
  • Inaba T, Matsushime H, Valentine M, Roussel MF, Sherr CJ, Look AT. Genomic organization, chromosomal localization, and independent expression of human cyclin D genes. Genomics. 1992 Jul;13(3):565–574. [PubMed]
  • Simon AM, Goodenough DA, Li E, Paul DL. Female infertility in mice lacking connexin 37. Nature. 1997 Feb 6;385(6616):525–529. [PubMed]
  • Stevanović M, Lovell-Badge R, Collignon J, Goodfellow PN. SOX3 is an X-linked gene related to SRY. Hum Mol Genet. 1993 Dec;2(12):2013–2018. [PubMed]
  • Conway GS, Hettiarachchi S, Murray A, Jacobs PA. Fragile X premutations in familial premature ovarian failure. Lancet. 1995 Jul 29;346(8970):309–310. [PubMed]
  • Mattison DR, Evans MI, Schwimmer WB, White BJ, Jensen B, Schulman JD. Familial premature ovarian failure. Am J Hum Genet. 1984 Nov;36(6):1341–1348. [PubMed]
  • Bell MV, Hirst MC, Nakahori Y, MacKinnon RN, Roche A, Flint TJ, Jacobs PA, Tommerup N, Tranebjaerg L, Froster-Iskenius U, et al. Physical mapping across the fragile X: hypermethylation and clinical expression of the fragile X syndrome. Cell. 1991 Feb 22;64(4):861–866. [PubMed]
  • Meijer H, de Graaff E, Merckx DM, Jongbloed RJ, de Die-Smulders CE, Engelen JJ, Fryns JP, Curfs PM, Oostra BA. 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. [PubMed]
  • Cronister A, Schreiner R, Wittenberger M, Amiri K, Harris K, Hagerman RJ. Heterozygous fragile X female: historical, physical, cognitive, and cytogenetic features. Am J Med Genet. 1991 Feb-Mar;38(2-3):269–274. [PubMed]
  • Schwartz CE, Dean J, Howard-Peebles PN, Bugge M, Mikkelsen M, Tommerup N, Hull C, Hagerman R, Holden JJ, Stevenson RE. Obstetrical and gynecological complications in fragile X carriers: a multicenter study. Am J Med Genet. 1994 Jul 15;51(4):400–402. [PubMed]
  • Knight SJ, Voelckel MA, Hirst MC, Flannery AV, Moncla A, Davies KE. Triplet repeat expansion at the FRAXE locus and X-linked mild mental handicap. Am J Hum Genet. 1994 Jul;55(1):81–86. [PubMed]
  • Murray A, Youings S, Dennis N, Latsky L, Linehan P, McKechnie N, Macpherson J, Pound M, Jacobs P. Population screening at the FRAXA and FRAXE loci: molecular analyses of boys with learning difficulties and their mothers. Hum Mol Genet. 1996 Jun;5(6):727–735. [PubMed]
  • Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 Feb 11;16(3):1215–1215. [PMC free article] [PubMed]
  • Rousseau F, Heitz D, Biancalana V, Blumenfeld S, Kretz C, Boué J, Tommerup N, Van Der Hagen C, DeLozier-Blanchet C, Croquette MF, et al. Direct diagnosis by DNA analysis of the fragile X syndrome of mental retardation. N Engl J Med. 1991 Dec 12;325(24):1673–1681. [PubMed]
  • Rousseau F, Rouillard P, Morel ML, Khandjian EW, 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. [PubMed]
  • Davis BM, McCurrach ME, Taneja KL, Singer RH, Housman DE. Expansion of a CUG trinucleotide repeat in the 3' untranslated region of myotonic dystrophy protein kinase transcripts results in nuclear retention of transcripts. Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7388–7393. [PubMed]
  • Bächner D, Manca A, Steinbach P, Wöhrle D, Just W, Vogel W, Hameister H, Poustka A. Enhanced expression of the murine FMR1 gene during germ cell proliferation suggests a special function in both the male and the female gonad. Hum Mol Genet. 1993 Dec;2(12):2043–2050. [PubMed]

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