鉴定新型纯合错义突变和缺失突变导致克什米尔人群少精子症不育。

Identification of novel homozygous missense and deletion mutations manifesting oligospermia infertility in Kashmiri population.

机构信息

School of Environment and Safety Engineering, Jiangsu University, Zhenjiang, China.

State key Laboratory of Environmental Chemistry and Ecotoxicology and Material of Water Treatment, Suzhou University of Science and Technology, Suzhou, China.

出版信息

J Gene Med. 2024 Jan;26(1):e3589. doi: 10.1002/jgm.3589. Epub 2023 Aug 30.

DOI:10.1002/jgm.3589

PMID:37649129

Abstract

BACKGROUND

Human male infertility has a lot of known molecular components that have an accurate diagnosis, such as Y chromosome deletion and monogenic causes. Only 4% of all infertile males are diagnosed with genetic causes, while 60-70% of infertile men remain without an accurate diagnosis and are classified as unexplained. Oligospermia is a major cause of human male infertility. Its etiology and pathogenesis are linked to genetic abnormalities. The majority of genetic causes related to human male infertility remain unclear.

RESULTS

Generally, we found a significant association between the specific type of disease and gender (p = 0.003), and the regression value (R ) for this association was 0.75. Association of the type of disease with body mass index was not significant (p = 0.34). There was no statistically significant difference (p = 0.40) among disease types with patients occupations. All explored mutations are listed for primary and secondary infertility in relation to the oligospermia condition. p.Arg286X is the outcome of a mismatch mutation in which the nucleotide change resulted in the substitution of Arg (arginine) amino acid with X (any amino acid) at position 286 in the Hyal3 gene of primary infertile patients having oligospermia. In primary infertile patients with the p.Arg286X mutation, a frameshift deletion mutation was also found just after the 25 nucleotide sequences of the Hyal3 genes of the second mutated exon. This deletion mutation was only detected in patients with primary infertility and was not found in people with secondary infertility or healthy controls. The other mutations in secondary infertile patients with oligospermia were: p.Lys168Ser, replacement of lysine (Lys) with serine (Ser) at position 168; p.Lys168The, replacement of lysine (Lys) with threonine (The) at position 168; p.His113X, substitution of histidine (His) with an unknown amino acid (X) at position 113; p.Pro162X, substitution of proline (Pro) with an unknown amino acid (X) at position 162; and p.Phe157X, phenylalanine (Phe) substitution with an unknown amino acid (X) at position 157.

CONCLUSION

This study clarifies the site of novel mismatch and frameshift deletion mutations in the Hyal3 gene in primary infertile oligospermia patients.

摘要

背景

人类男性不育症有许多已知的分子成分，这些成分可以得到准确的诊断，例如 Y 染色体缺失和单基因病因。只有 4%的不育男性被诊断为遗传原因，而 60-70%的不育男性仍然没有明确的诊断，被归类为不明原因。少精子症是人类男性不育的主要原因。其病因和发病机制与遗传异常有关。大多数与人类男性不育相关的遗传原因仍不清楚。

结果

一般来说，我们发现特定类型的疾病与性别之间存在显著关联（p=0.003），并且这种关联的回归值（R）为 0.75。疾病类型与体重指数之间的关联不显著（p=0.34）。疾病类型与患者职业之间没有统计学上的显著差异（p=0.40）。所有探索到的突变都与少精子症相关的原发性和继发性不育有关。p.Arg286X 是错配突变的结果，核苷酸的改变导致在 Hyal3 基因的第 286 位上，精氨酸（Arg）氨基酸被 X（任何氨基酸）取代，在患有少精子症的原发性不育患者中。在原发性不育患者中，我们还发现了 p.Arg286X 突变后第 25 个核苷酸序列的移码缺失突变。这种缺失突变仅在原发性不育患者中检测到，在继发性不育患者和健康对照中均未检测到。在患有少精子症的继发性不育患者中还发现了其他突变：p.Lys168Ser，赖氨酸（Lys）在第 168 位被丝氨酸（Ser）取代；p.Lys168The，赖氨酸（Lys）在第 168 位被苏氨酸（The）取代；p.His113X，组氨酸（His）在第 113 位被未知氨基酸（X）取代；p.Pro162X，脯氨酸（Pro）在第 162 位被未知氨基酸（X）取代；和 p.Phe157X，苯丙氨酸（Phe）在第 157 位被未知氨基酸（X）取代。