Identification and functional analysis of a rare variant of gene DHX37 in a patient with 46,XY disorders of sex development.

IF 1.5 4区医学 Q4 GENETICS & HEREDITY

Molecular Genetics & Genomic Medicine Pub Date : 2024-05-01 DOI:10.1002/mgg3.2453

Wei Jiang, Jing Yu, Yu Mao, Yunman Tang, Li Cao, Qin Du, Jianan Li, Jiyun Yang

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引用次数: 0

Abstract

Background: 46,XY sex reversal 11 (SRXY11) [OMIM#273250] is characterized by genital ambiguity that may range from mild male genital defects to gonadal sex reversal in severe cases. DHX37 is an RNA helicase that has recently been reported as a cause of SRXY11. So far, a total of 21 variants in DHX37 have been reported in 58 cases with 46,XY disorders of sex development (DSD).

Methods: Whole exome sequencing (WES) was conducted to screen for variations in patients with 46,XY DSD. The subcellular localization of mutant DHX37 proteins was detected by immunofluorescence. And the levels of mutant DHX37 proteins were detected via Western blotting.

Results: A novel pathogenic variant of DHX37 was identified in a patient with 46,XY DSD c.2012G > C (p.Arg671Thr). Bioinformatics analysis showed that the protein function of the variant was impaired. Compared with the structure of the wild-type DHX37 protein, the number of hydrogen bonds and interacting amino acids of the variant protein were changed to varying degrees. In vitro assays revealed that the variant had no significant effect on the intracellular localization of the protein but significantly reduced the expression level of the protein.

Conclusions: Our finding further expands the spectrum of the DHX37 variant and could assist in the molecular diagnosis of 46,XY DSD patients.

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在一名 46,XY 性别发育障碍患者身上发现 DHX37 基因罕见变体并对其进行功能分析。

背景：46,XY性别反转11（SRXY11）[OMIM#273250]的特征是生殖器不明确，轻者为男性生殖器缺陷，重者为性腺性别反转。DHX37 是一种 RNA 螺旋酶，最近有报道称它是 SRXY11 的病因之一。迄今为止，在 58 例 46,XY 性别发育障碍（DSD）病例中，共发现了 21 个 DHX37 变异：方法：对46,XY DSD患者进行全外显子组测序（WES）以筛选变异。方法：采用全外显子组测序（WES）方法筛查46,XY DSD患者的变异。免疫荧光法检测了突变 DHX37 蛋白的亚细胞定位，Western 印迹法检测了突变 DHX37 蛋白的水平：结果：在一名46,XY DSD c.2012G > C（p.Arg671Thr）患者体内发现了一种新的DHX37致病变体。生物信息学分析表明，该变异体的蛋白质功能受损。与野生型 DHX37 蛋白的结构相比，变异蛋白的氢键数量和相互作用氨基酸发生了不同程度的变化。体外实验显示，变体对蛋白质的胞内定位没有明显影响，但却显著降低了蛋白质的表达水平：我们的发现进一步扩大了DHX37变体的范围，有助于46,XY DSD患者的分子诊断。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Genetics & Genomic Medicine Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

4.20

自引率

0.00%

发文量

241

审稿时长

14 weeks

期刊介绍： Molecular Genetics & Genomic Medicine is a peer-reviewed journal for rapid dissemination of quality research related to the dynamically developing areas of human, molecular and medical genetics. The journal publishes original research articles covering findings in phenotypic, molecular, biological, and genomic aspects of genomic variation, inherited disorders and birth defects. The broad publishing spectrum of Molecular Genetics & Genomic Medicine includes rare and common disorders from diagnosis to treatment. Examples of appropriate articles include reports of novel disease genes, functional studies of genetic variants, in-depth genotype-phenotype studies, genomic analysis of inherited disorders, molecular diagnostic methods, medical bioinformatics, ethical, legal, and social implications (ELSI), and approaches to clinical diagnosis. Molecular Genetics & Genomic Medicine provides a scientific home for next generation sequencing studies of rare and common disorders, which will make research in this fascinating area easily and rapidly accessible to the scientific community. This will serve as the basis for translating next generation sequencing studies into individualized diagnostics and therapeutics, for day-to-day medical care. Molecular Genetics & Genomic Medicine publishes original research articles, reviews, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented.