A Homozygous Missense Variant in Hedgehog Acyltransferase (HHAT) Gene Associated with 46,XY Gonadal Dysgenesis.

IF 2.4 4区医学 Q2 DEVELOPMENTAL BIOLOGY

Sexual Development Pub Date : 2022-01-01 DOI:10.1159/000520366

Inas Mazen, Alaa Kamel, Kenneth McElreavey, Anu Bashamboo, Aya Elaidy, Mohamed S Abdel-Hamid

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引用次数: 2

Abstract

Introduction: Disorders of gonadal development represent a clinically and genetically heterogeneous group of DSD, and the etiology in many cases remains unknown, indicating that our knowledge of factors controlling sex determination is still limited.

Methods: We describe a 46,XY DSD patient from Egypt. The patient was reared as female, born to consanguineous parents, and was referred to us at the age of 5 years because of ambiguous genitalia. On examination, the girl was microcephalic (head circumference -3 SD), but her height and weight were normal for her age and sex.

Results: Exome sequencing identified a homozygous variant in the hedgehog acyltransferase (HHAT) gene, which encodes an enzyme that is required for multimerization and signaling potency of the hedgehog secreted proteins. The variant is a novel homozygous missense change c.1329C>A (p.N443K), located within transmembrane domain 9, which segregated with the phenotype in the family.

Discussion/conclusion: Our results expand the phenotypic spectrum associated with HHAT variants to include 46,XY gonadal dysgenesis and reinforce the role of exome sequencing in unraveling new genes that play a pivotal role in sexual development.

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与46,xy性腺发育不良相关的Hedgehog酰基转移酶(HHAT)基因纯合错义变异。

性腺发育障碍是DSD的一个临床和遗传异质性群体，许多病例的病因尚不清楚，这表明我们对控制性别决定的因素的了解仍然有限。方法:我们描述了一位来自埃及的46,xy DSD患者。患者被视为女性，由近亲父母所生，并在5岁时因生殖器模糊而被转介到我们这里。经检查，该女孩为小头症(头围- 3sd)，但其身高和体重在其年龄和性别中是正常的。结果:外显子组测序鉴定出刺猬酰基转移酶(HHAT)基因的纯合变异，该基因编码一种酶，该酶是刺猬分泌蛋白的多聚和信号转导能力所必需的。该变异是一个新的纯合错义突变c.1329C> a (p.N443K)，位于跨膜结构域9内，在家族中与表型分离。讨论/结论:我们的研究结果扩大了与HHAT变异相关的表型谱，包括46,xy性腺发育障碍，并加强了外显子组测序在揭示在性发育中起关键作用的新基因中的作用。

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

Sexual Development 生物-发育生物学

CiteScore

4.00

自引率

4.30%

发文量

审稿时长

>12 weeks

期刊介绍： Recent discoveries in experimental and clinical research have led to impressive advances in our knowledge of the genetic and environmental mechanisms governing sex determination and differentiation, their evolution as well as the mutations or endocrine and metabolic abnormalities that interfere with normal gonadal development. ‘Sexual Development’ provides a unique forum for this rapidly expanding field. Its broad scope covers all aspects of genetics, molecular biology, embryology, endocrinology, evolution and pathology of sex determination and differentiation in humans and animals. It publishes high-quality original research manuscripts, review articles, short reports, case reports and commentaries. An internationally renowned and multidisciplinary editorial team of three chief editors, ten prominent scientists serving as section editors, and a distinguished panel of editorial board members ensures fast and author-friendly editorial processing and peer reviewing.