Identification of a novel splicing variant of thyroid hormone receptor interaction protein 13 (TRIP13) in female infertility characterized by oocyte maturation arrest
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引用次数: 0
Abstract
Purpose
As a cause of primary female infertility, oocyte maturation arrest (OMA) is characterized by failure to obtain mature oocytes due to abnormal meiosis. We aimed to identify pathogenic variants in two sisters with OMA phenotype from a non-consanguineous family.
Methods
Whole-exome sequencing and Sanger sequencing were conducted to identify and validate the disease-causing gene variant. Additionally, we performed a minigene assay, quantitative reverse transcription PCR, and Western blotting to assess the effects of the variant.
Results
We identified a novel homozygous splicing variant (c.1021-11T>C) in TRIP13, which followed a recessive inheritance pattern. Minigene assay showed that the variant could disrupt the integrity of TRIP13 mRNA, as evidenced by the production of an alternative transcript with intron10 intermediate retention of 79 bp. Compared to normal controls, the expression of TRIP13 mRNA and abundance of TRIP13 protein were also significantly decreased in Epstein-Barr virus-immortalized lymphoblastoid cells derived from affected individuals.
Conclusion
Our findings confirm the contribution of genetic factors to OMA and expand the mutation spectrum of TRIP13 in female infertility.
期刊介绍：
The Journal of Assisted Reproduction and Genetics publishes cellular, molecular, genetic, and epigenetic discoveries advancing our understanding of the biology and underlying mechanisms from gametogenesis to offspring health. Special emphasis is placed on the practice and evolution of assisted reproduction technologies (ARTs) with reference to the diagnosis and management of diseases affecting fertility. Our goal is to educate our readership in the translation of basic and clinical discoveries made from human or relevant animal models to the safe and efficacious practice of human ARTs. The scientific rigor and ethical standards embraced by the JARG editorial team ensures a broad international base of expertise guiding the marriage of contemporary clinical research paradigms with basic science discovery. JARG publishes original papers, minireviews, case reports, and opinion pieces often combined into special topic issues that will educate clinicians and scientists with interests in the mechanisms of human development that bear on the treatment of infertility and emerging innovations in human ARTs. The guiding principles of male and female reproductive health impacting pre- and post-conceptional viability and developmental potential are emphasized within the purview of human reproductive health in current and future generations of our species.
The journal is published in cooperation with the American Society for Reproductive Medicine, an organization of more than 8,000 physicians, researchers, nurses, technicians and other professionals dedicated to advancing knowledge and expertise in reproductive biology.
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