X שביר

יש מאמרים רבים על הקשר בין X- שביר ואי ספיקת שחלות מוקדמת (הסיכון גדל פי 20). פרט לכך אני לא מכיר הרבה מחקרים ביחס לפריון וכרומוזום X שביר. סקירה טובה: Am J Med Genet 2000 Fall;97(3):189-94 Premature ovarian failure in the fragile X syndrome. Sherman SL. Department of Genetics, Emory University School of Medicine, 1462 Clifton Road, Atlanta, GA 30322, USA. [email protected] The full mutation leading to the fragile X syndrome is a dynamic trinucleotide repeat located in the 5' untranslated region of the FMR1 gene. The premutation allele contains approximately 60 to 199 repeats, is unstable, and originally not considered detrimental; that is, there did not appear to be a phenotype consequence of the long repeat tract. However, in the late 1980s and early 1990s, preliminary findings suggested that nonimpaired heterozygotes were at risk of early menopause and increased rates of twinning, both indications of ovarian failure. Once premutation carriers could be distinguished from full mutation carriers, this phenotype was found to be restricted to premutation carriers only. Based on the recent studies reviewed here, approximately 21% of premutation carriers have premature ovarian failure (POF) compared to only 1% in the general population, or a relative risk of 21. Moreover, among women with idiopathic sporadic or the more rare form of familial POF, approximately 2% and 14%, respectively, carry the premutation. To date, data supporting increased twinning rates are conflicting and need to be resolved. Neither the underlying cellular pathophysiology of POF caused by the premutation allele nor molecular mechanism underlying the presence of the long repeat tract of the premutation allele is understood. Irrespective, women who carry the premutation allele should have not only genetic counseling but also fertility counseling to ensure that they reach their goals for reproduction. מאמרים עדכניים: Am J Med Genet 1999 Apr 2;83(4):322-5 Fragile X premutation is a significant risk factor for premature ovarian failure: the International Collaborative POF in Fragile X study--preliminary data. Allingham-Hawkins DJ, Babul-Hirji R, Chitayat D, Holden JJ, Yang KT, Lee C, Hudson R, Gorwill H, Nolin SL, Glicksman A, Jenkins EC, Brown WT, Howard-Peebles PN, Becchi C, Cummings E, Fallon L, Seitz S, Black SH, Vianna-Morgante AM, Costa SS, Otto PA, Mingroni-Netto RC, Murray A, Webb J, Vieri F, et al. [email protected] The preliminary results of an international collaborative study examining premature menopause in fragile X carriers are presented. A total of 760 women from fragile X families was surveyed about their fragile X carrier status and their menstrual and reproductive histories. Among the subjects, 395 carried a premutation, 128 carried a full mutation, and 237 were noncarriers. Sixty-three (16%) of the premutation carriers had experienced menopause prior to the age of 40 compared with none of the full mutation carriers and one (0.4%) of the controls. Based on these preliminary data, there is a significant association between fragile X premutation carrier status and premature menopause. Hum Reprod 2000 Jan;15(1):197-202 Related Articles, Links Comment in: Hum Reprod. 2000 Aug;15(8):1874-5. Association between idiopathic premature ovarian failure and fragile X premutation. Marozzi A, Vegetti W, Manfredini E, Tibiletti MG, Testa G, Crosignani PG, Ginelli E, Meneveri R, Dalpra L. Department of Biology and Genetics for Medical Sciences, University of Milan, Via Viotti 3/5, 20133 Milan, Italy. A total of 106 women affected by premature ovarian failure (POF) were evaluated for fragile X (FRAXA) premutation. The POF patients were classified as having a familial condition (33 women), at least one relative with early menopause (12 women), or a sporadic condition (61 women). The FRAXA premutation was only detected in patients with familial (four out of 33) or sporadic POF (two out of 61). In general, the results obtained indicated that the prevalence [six out of 106, 6%, 95% confidence interval (CI) 3-11%] of FRAXA premutation is significantly higher in women affected by POF than expected (P = 1.24x10(-3)), suggesting a phenotype consequence of the premutation alleles. This relationship is more convincingly derived from the observation in two analysed pedigrees of a co-segregation between FRAXA and POF. These findings suggest a possible involvement of premutated alleles in ovarian failure, and indicate the utility of POF families screening for FRAXA premutation in order to prevent the transmission of mental retardation syndrome.