Recurrent Pregnancy Loss and Infertility Due to A New Mutation in an Iranian Family

سال انتشار: 1398
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 334

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شناسه ملی سند علمی:

RROYAN20_350

تاریخ نمایه سازی: 29 مهر 1398

چکیده مقاله:

Background: Recurrent pregnancy loss (RPL) is a multifacto-rial disorder and defined as two or more consecutive miscar-riages that affects up to 5% of clinical pregnancies. Several factors are associated with RPL, however, in 35–60% of mis-carriages the etiology remains unexplained. In recent years, the advent of high throughput technologies, such as next generation sequencing (NGS), have provided new capabilities for discov-ery of too small genetic changes in hereditary diseases such as RPL. In this study, we used whole-exome sequencing approach (WES) to find pathogenic variants in an Iranian family with RPL history.Materials and Methods: After finding an affected family, clinical investigations were done. Genomic DNA was extract-ed from blood samples and qualified and quantified DNA was subjected to WES. DNA sequencing was done by HiSeq 2000 from Illumina®, and the reads were aligned to the human ref-erence genome (hg19). After variant calling and filtering, the variations that scored as ‘tolerated’ and ‘benign’ were excluded. And at the end, a candidate variant was confirmed by sanger sequencing method in family members.Results: Clinical investigations such as thrombophilia’s, uter-ine anatomy, hormonal /endocrine disorders, immunologic fac-tors, infections, karyotyping and Microarray-based compara-tive genomic hybridization (array CGH) in the proband were normal. A new missense mutation was identified in 100% ana-lyzed subjects with RPL history.Conclusion: In conclusion, to our knowledge, this is the first study investigating genetic variations in RPL through a family-based exome sequencing which found a new mutation in 3 outof 3 (100%) RPL patients. Our results expand our knowledge on the involvement of a new gene in human pregnancy com-plications. Indeed, our findings confirm that WES is a useful alternative approach to reach a genetic diagnosis in patients.

نویسندگان

NS Fatemi

Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran. Department of Genetics and Molecular Medicine, School of Medi-cine, Zanjan University of Medical Sciences (ZUMS), Zanjan,

F Ray Pierre

Genetic Epigenetic and Therapies of Infertility, Institute for Ad-vanced Biosciences, University of Grenoble, Alpes, France.. UF de Biochimie Génétique et Moléculaire, Grenoble, France

A Amiri-Yekta

Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

F Ramezanali

Department of Endocrinology and Female Infertility, Reproduc-tive Biomedicine Research Center, Royan Institute for Reproduc-tive Biomedicine, ACECR, Tehran, Iran