Deepika Delsa Dean1, Sarita Agarwal2,3, Srinivasan Muthuswamy1,4. 1. Dept of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, U.P., India. 2. Dept of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, U.P., India. saritasgpgi@gmail.com. 3. Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, 226014, India. saritasgpgi@gmail.com. 4. Department of Life Science, National Institute of Technology Rourkela, Odisha, 769008, India.
Abstract
INTRODUCTION: Recurrent spontaneous abortion is a multifactorial disorder and till date, various factors have been attributed in its pathogenesis. Still, approximately 50% of RSA cases remain unexplained. Premutation (PM) expanded allele of fragile-X mental retardation 1 (FMR1) gene is known to contribute to ovarian dysfunction in 20% of the cases. Recently, the link between expanded FMR1 allele and recurrent miscarriages has been reported. METHOD: In the present prospective case-control study, we have investigated the status of CGG repeat size at 5'UTR of the FMR1 gene in women with unexplained RSA in comparison to age-matched healthy control women (n = 100 each). The genomic DNA from these samples was subjected to molecular analysis for characterization of CGG repeat size and composition at FMR1 gene RESULTS: As compared to the control women, the RSA women cohort had a higher frequency of carriers with alleles in gray zone (GZ) and expanded PM range, i.e., 2% (2/100) versus 5% (5/100), respectively. Also, the RSA cohort had a significantly higher number of normal alleles with ≥ 35 CGG repeats (24 out of 200 alleles) as compared to control cohort (8 out of 200 alleles). The number of larger FMR1 alleles with pure CGG repeat tract was found to be significantly higher (P = 0.0063) in the RSA cohort (15 out of 200 alleles) as compared to that in control cohort (3 out of 200 alleles). CONCLUSION: Henceforth, the CGG expanded uninterrupted FMR1 allele might be associated with recurrent abortions and may help to explain many of these unexplained cases.
INTRODUCTION: Recurrent spontaneous abortion is a multifactorial disorder and till date, various factors have been attributed in its pathogenesis. Still, approximately 50% of RSA cases remain unexplained. Premutation (PM) expanded allele of fragile-X mental retardation 1 (FMR1) gene is known to contribute to ovarian dysfunction in 20% of the cases. Recently, the link between expanded FMR1 allele and recurrent miscarriages has been reported. METHOD: In the present prospective case-control study, we have investigated the status of CGG repeat size at 5'UTR of the FMR1 gene in women with unexplained RSA in comparison to age-matched healthy control women (n = 100 each). The genomic DNA from these samples was subjected to molecular analysis for characterization of CGG repeat size and composition at FMR1 gene RESULTS: As compared to the control women, the RSAwomen cohort had a higher frequency of carriers with alleles in gray zone (GZ) and expanded PM range, i.e., 2% (2/100) versus 5% (5/100), respectively. Also, the RSA cohort had a significantly higher number of normal alleles with ≥ 35 CGG repeats (24 out of 200 alleles) as compared to control cohort (8 out of 200 alleles). The number of larger FMR1 alleles with pure CGG repeat tract was found to be significantly higher (P = 0.0063) in the RSA cohort (15 out of 200 alleles) as compared to that in control cohort (3 out of 200 alleles). CONCLUSION: Henceforth, the CGG expanded uninterrupted FMR1 allele might be associated with recurrent abortions and may help to explain many of these unexplained cases.
Authors: Sindhu K Srinivas; Yujie Ma; Mary D Sammel; Doris Chou; Cindy McGrath; Samuel Parry; Michal A Elovitz Journal: Am J Obstet Gynecol Date: 2006-09 Impact factor: 8.661
Authors: Osman Ali; Ihssane Hakimi; Adil Chanana; My Abdellah Baba Habib; Khalid Guelzim; Jaouad Kouach; Driss Moussaoui Rahali; Mohammed Dehayeni Journal: Pan Afr Med J Date: 2015-11-10
Authors: Jiahui Huo; Qian Chen; Yutong Zhang; Nuo Li; Zhiyu Fu; Ning Ma; Nan Zheng; Nan Cui; Lu Li Journal: Front Genet Date: 2022-09-02 Impact factor: 4.772