OBJECTIVE: To study three molecular parameters (number of CGG repeats, X-inactivation ratio, and expression of FMR1 mRNA) in premutation carriers of fragile X syndrome with and without premature ovarian failure (POF) to find differences between these two groups that could be useful in reproductive counseling. DESIGN: A retrospective clinical and molecular genetic study of 42 known premutation carriers of fragile X syndrome aged 40 years or older, 25 with POF and 17 without. A blood sample to obtain mRNA was taken from all of them. They all lived in five autonomous communities in northern Spain. RESULTS: Although the relationship among mRNA levels, X-inactivation ratio, and CGG repeats seems to be similar both in women with POF and in those without: in women with POF, the effect of the CGG repeats on the mRNA levels was statistically significant (P = 0.0437), but in women without POF, it was not (P = 0.0724). Moreover, we confirmed previous results on the nonlinear association between CGG repeat number and the manifestation of POF, showing that the likelihood of having POF was significantly higher with fewer than 100 CGG repeats compared with 100 or more CGG repeats (odds ratio = 13.09, P = 0.0240). CONCLUSIONS: Our present work suggests that mRNA and X-inactivation studies in blood are not relevant in predicting POF in female premutation carriers of fragile X syndrome. However, having a permutation of fewer than 100 repeats could represent a significant risk of POF.
OBJECTIVE: To study three molecular parameters (number of CGG repeats, X-inactivation ratio, and expression of FMR1 mRNA) in premutation carriers of fragile X syndrome with and without premature ovarian failure (POF) to find differences between these two groups that could be useful in reproductive counseling. DESIGN: A retrospective clinical and molecular genetic study of 42 known premutation carriers of fragile X syndrome aged 40 years or older, 25 with POF and 17 without. A blood sample to obtain mRNA was taken from all of them. They all lived in five autonomous communities in northern Spain. RESULTS: Although the relationship among mRNA levels, X-inactivation ratio, and CGG repeats seems to be similar both in women with POF and in those without: in women with POF, the effect of the CGG repeats on the mRNA levels was statistically significant (P = 0.0437), but in women without POF, it was not (P = 0.0724). Moreover, we confirmed previous results on the nonlinear association between CGG repeat number and the manifestation of POF, showing that the likelihood of having POF was significantly higher with fewer than 100 CGG repeats compared with 100 or more CGG repeats (odds ratio = 13.09, P = 0.0240). CONCLUSIONS: Our present work suggests that mRNA and X-inactivation studies in blood are not relevant in predicting POF in female premutation carriers of fragile X syndrome. However, having a permutation of fewer than 100 repeats could represent a significant risk of POF.
Authors: Marsha Mailick; Jinkuk Hong; Jan Greenberg; Leann Smith Dawalt; Mei Wang Baker; Paul J Rathouz Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2017-04-13 Impact factor: 3.568
Authors: M A Spath; T B Feuth; E G Allen; A P T Smits; H G Yntema; A Geurts van Kessel; D D M Braat; S L Sherman; C M G Thomas Journal: Hum Reprod Date: 2011-05-15 Impact factor: 6.918
Authors: Marsha R Mailick; Jinkuk Hong; Jan Greenberg; Leann Smith; Stephanie Sherman Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2014-10-25 Impact factor: 3.568
Authors: Igor Albizua; Benjamin L Rambo-Martin; Emily G Allen; Weiya He; Ashima S Amin; Stephanie L Sherman Journal: Am J Med Genet A Date: 2017-09-21 Impact factor: 2.802
Authors: M Friedman-Gohas; M Kirshenbaum; A Michaeli; N Domniz; S Elizur; H Raanani; R Orvieto; Y Cohen Journal: J Assist Reprod Genet Date: 2020-02-24 Impact factor: 3.412
Authors: D Z Loesch; M Q Bui; E Hammersley; A Schneider; E Storey; P Stimpson; T Burgess; D Francis; H Slater; F Tassone; R J Hagerman; D Hessl Journal: Clin Genet Date: 2014-02-17 Impact factor: 4.438
Authors: David E Godler; Danuta Z Loesch; Richard Huggins; Lavinia Gordon; Howard R Slater; Freya Gehling; Trent Burgess; K H Andy Choo Journal: BMC Clin Pathol Date: 2009-06-09