DHX37 Variant is One of Common Genetic Causes in Japanese Patients with Testicular Regression Syndrome / Partial Gonadal Dysgenesis without Müllerian Derivatives.

IF 2.6 3区 医学 Q3 ENDOCRINOLOGY & METABOLISM
Kazuhiro Shimura, Yosuke Ichihashi, Satsuki Nakano, Takeshi Sato, Takashi Hamajima, Keita Numasawa, Satoshi Narumi, Tomonobu Hasegawa, Tomohiro Ishii
{"title":"DHX37 Variant is One of Common Genetic Causes in Japanese Patients with Testicular Regression Syndrome / Partial Gonadal Dysgenesis without Müllerian Derivatives.","authors":"Kazuhiro Shimura, Yosuke Ichihashi, Satsuki Nakano, Takeshi Sato, Takashi Hamajima, Keita Numasawa, Satoshi Narumi, Tomonobu Hasegawa, Tomohiro Ishii","doi":"10.1159/000537761","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>The testicular regression syndrome (TRS) is a form of differences of sex development (DSD) in which the testes differentiate and function during early embryonic development, but subsequently regress. The clinical phenotype of TRS often overlaps with that of partial gonadal dysgenesis (PGD). Previous studies have demonstrated a causal association between TRS/PGD and heterozygous missense variants of DHX37.</p><p><strong>Methods: </strong>We enrolled 11 Japanese 46,XY individuals (from 10 families) with TRS/PGD who exhibited undetected or hypoplastic testes, Müllerian duct regression, and low serum testosterone or anti-Müllerian hormone levels. The subjects underwent targeted sequencing of 36 known causative genes for DSD, PCR-based Sanger sequencing of DHX37, or whole exome sequencing.</p><p><strong>Results: </strong>Previously described pathogenic variants or novel nonsense variants (SRY, NR5A1, and DMRT1) were observed in four out of 10 families. Additionally, we identified two heterozygous rare variants of DHX37 in four families: a previously reported pathogenic variant (c.923G>A, p.Arg308Gln) in three and a novel likely pathogenic variant (c.1882A>C, p.Thr628Pro) in one. The external genitalia of patients with the DHX37 variants varied from female-type to male-type without micropenis. Eighty percent of Japanese patients with TRS/PGD had monogenic disorders including DHX37 variant being the most commonly identified (40%). The external or internal genital phenotype of TRS/PGD overlaps between DHX37 variant carriers and others.</p><p><strong>Conclusions: </strong>DHX37 variant is one of common genetic causes in Japanese patients with TRS/PGD without Müllerian derivatives. Genetic test is helpful in detecting DHX37-related TRS/PGD, because of the phenotypic diversity of the external genitalia in this disorder.</p>","PeriodicalId":13025,"journal":{"name":"Hormone Research in Paediatrics","volume":null,"pages":null},"PeriodicalIF":2.6000,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hormone Research in Paediatrics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000537761","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0

Abstract

Introduction: The testicular regression syndrome (TRS) is a form of differences of sex development (DSD) in which the testes differentiate and function during early embryonic development, but subsequently regress. The clinical phenotype of TRS often overlaps with that of partial gonadal dysgenesis (PGD). Previous studies have demonstrated a causal association between TRS/PGD and heterozygous missense variants of DHX37.

Methods: We enrolled 11 Japanese 46,XY individuals (from 10 families) with TRS/PGD who exhibited undetected or hypoplastic testes, Müllerian duct regression, and low serum testosterone or anti-Müllerian hormone levels. The subjects underwent targeted sequencing of 36 known causative genes for DSD, PCR-based Sanger sequencing of DHX37, or whole exome sequencing.

Results: Previously described pathogenic variants or novel nonsense variants (SRY, NR5A1, and DMRT1) were observed in four out of 10 families. Additionally, we identified two heterozygous rare variants of DHX37 in four families: a previously reported pathogenic variant (c.923G>A, p.Arg308Gln) in three and a novel likely pathogenic variant (c.1882A>C, p.Thr628Pro) in one. The external genitalia of patients with the DHX37 variants varied from female-type to male-type without micropenis. Eighty percent of Japanese patients with TRS/PGD had monogenic disorders including DHX37 variant being the most commonly identified (40%). The external or internal genital phenotype of TRS/PGD overlaps between DHX37 variant carriers and others.

Conclusions: DHX37 variant is one of common genetic causes in Japanese patients with TRS/PGD without Müllerian derivatives. Genetic test is helpful in detecting DHX37-related TRS/PGD, because of the phenotypic diversity of the external genitalia in this disorder.

DHX37变异是日本睾丸退化综合征/部分性腺发育不良(无Müllerian衍生物)患者的常见遗传原因之一。
简介睾丸退行综合征(TRS)是性别发育差异(DSD)的一种形式,即睾丸在胚胎发育早期分化并发挥功能,但随后退行。TRS的临床表型往往与部分性腺发育不良(PGD)重叠。以往的研究表明,TRS/PGD 与 DHX37 的杂合子错义变异之间存在因果关系:我们招募了 11 名日本 46,XY 型 TRS/PGD 患者(来自 10 个家庭),他们的睾丸未检测到或发育不全、穆勒氏管退化、血清睾酮或抗穆勒氏管激素水平较低。受试者接受了36个已知DSD致病基因的靶向测序、基于PCR的DHX37 Sanger测序或全外显子组测序:结果:在 10 个家庭中,有 4 个家庭发现了之前描述过的致病变异或新型无义变异(SRY、NR5A1 和 DMRT1)。此外,我们还在 4 个家族中发现了 DHX37 的两个杂合罕见变异:3 个家族中发现了之前报道的致病变异(c.923G>A,p.Arg308Gln),1 个家族中发现了可能的新型致病变异(c.1882A>C,p.Thr628Pro)。DHX37变异体患者的外生殖器从女性型到男性型不等,但无小阴茎。80%的日本 TRS/PGD 患者患有单基因遗传疾病,其中 DHX37 变体是最常见的变体(40%)。DHX37变异体携带者与其他患者的TRS/PGD外生殖器或内生殖器表型重叠:结论:DHX37 变体是日本 TRS/PGD 患者(无穆勒氏衍生物)的常见遗传病因之一。由于外生殖器表型的多样性,基因检测有助于发现与 DHX37 相关的 TRS/PGD。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Hormone Research in Paediatrics
Hormone Research in Paediatrics ENDOCRINOLOGY & METABOLISM-PEDIATRICS
CiteScore
4.90
自引率
6.20%
发文量
88
审稿时长
4-8 weeks
期刊介绍: The mission of ''Hormone Research in Paediatrics'' is to improve the care of children with endocrine disorders by promoting basic and clinical knowledge. The journal facilitates the dissemination of information through original papers, mini reviews, clinical guidelines and papers on novel insights from clinical practice. Periodic editorials from outstanding paediatric endocrinologists address the main published novelties by critically reviewing the major strengths and weaknesses of the studies.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信