通过南印度人的全外显子组测序确定了磷酸丝氨酸磷酸酶(PSPH)基因突变与男性不育的新关联

IF 0.8 Q4 GENETICS & HEREDITY Meta Gene Pub Date : 2021-09-01 DOI:10.1016/j.mgene.2021.100897
Golnaz Shemshaki , Mohsen Najafi , Ashitha S. Niranjana Murthy , Suttur S. Malini
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引用次数: 0

摘要

男性不育症(MI)主要由生精失败引起,尽管经过多年的辅助生殖治疗,但仍有相当数量的病例是特发性的。少弱精子症(OA)是最严重的特发性心肌梗死形式之一,以精子活力和数量减少为条件。然而,其病理尚不清楚,但很少有遗传因素已确定。本研究的主要目的是发现严重OA患者生精基因的遗传变异。收集了250例心肌梗死患者的精液和血液样本。进行精液分析、核型分析和Y微缺失以保留纯粹特发性心肌梗死病例(n = 247)。共发现40例OA病例,其中4例重症病例进行全外显子组测序、生物信息学分析和通路分析,其余36例OA病例通过Sanger测序验证致病变异。我们在PSPH基因外显子5中发现了6个突变,其中4个突变被预测为致病性突变,2个突变被预测为破坏性突变。在这项研究中,我们提出了PSPH基因在它们不同的机制途径中的新作用。对参与l-丝氨酸生物合成的PSPH酶的详细途径分析表明,其功能障碍可能导致精子数量和精子活力下降。PSPH在引发OA中的假设功能已被描述。
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Novel association of PhosphoSerine PHosphatase (PSPH) gene mutations with male infertility identified through whole exome sequencing of South Indians

Male infertility (MI) is mainly caused by spermatogenic failure, and despite long years of assisted reproductive therapy, a significant number of cases remain idiopathic. Oligoasthenozoospermia (OA) is one of the most severe idiopathic MI forms, conditioned with decreased sperm motility and count. However, its pathology remains unclear, but few genetic factors have been identified. The main aim of this study was to find genetic variations in spermatogenic genes with severe OA. Semen and blood samples were collected from 250 MI subjects. Semen analysis, karyotyping, and Y microdeletion was performed to retain purely idiopathic MI cases (n = 247). 40 OA cases were identified, of which four severe cases were subjected to whole-exome sequencing, bioinformatics analyses, and pathway analysis, followed by validation of pathogenic variants in the remaining 36 OA cases through Sanger sequencing. We identified six variants in exon5 of gene PSPH, of which four variants were predicted to be pathogenic and two damaging mutations in exon4. In this study, we propose the novel role of the PSPH gene in their different mechanistic pathways. Detailed pathway analysis of enzyme PSPH involved in l-serine biosynthesis demonstrated that its dysfunction could cause a decrease in sperm count and sperm motility. The hypothesized function of PSPH in eliciting OA has been described.

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来源期刊
Meta Gene
Meta Gene Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
1.10
自引率
0.00%
发文量
20
期刊介绍: Meta Gene publishes meta-analysis, polymorphism and population study papers that are relevant to both human and non-human species. Examples include but are not limited to: (Relevant to human specimens): 1Meta-Analysis Papers - statistical reviews of the published literature of human genetic variation (typically linked to medical conditionals and/or congenital diseases) 2Genome Wide Association Studies (GWAS) - examination of large patient cohorts to identify common genetic factors that influence health and disease 3Human Genetics Papers - original studies describing new data on genetic variation in smaller patient populations 4Genetic Case Reports - short communications describing novel and in formative genetic mutations or chromosomal aberrations (e.g., probands) in very small demographic groups (e.g., family or unique ethnic group). (Relevant to non-human specimens): 1Small Genome Papers - Analysis of genetic variation in organelle genomes (e.g., mitochondrial DNA) 2Microbiota Papers - Analysis of microbiological variation through analysis of DNA sequencing in different biological environments 3Ecological Diversity Papers - Geographical distribution of genetic diversity of zoological or botanical species.
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