Two Novel and Two Recurrent Variants of the ADAR1 Gene in Three Chinese Families with Dyschromatosis Symmetrica Hereditaria.

IF 1.9 4区医学 Q3 DERMATOLOGY

Clinical, Cosmetic and Investigational Dermatology Pub Date : 2024-10-24 eCollection Date: 2024-01-01 DOI:10.2147/CCID.S477138

Yunxia Zhu, Deng Zhang, Liang Wu, Xiaoliang Ouyang, Shengcai Zhu, Xiuping Wang, Zhen Xiao, Yanping Tan, Chunming Li

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引用次数: 0

Abstract

Purpose: Dyschromatosis symmetrica hereditaria (DSH) is a rare autosomal dominant inherited pigmentary dermatosis. The gene responsible for DSH has been identified as adenosine deaminase acting on RNA1 (ADAR1). This study aimed to identify the causative variants in the ADAR1 gene in three Chinese families with DSH.

Patients and methods: Data and blood samples were collected from three Chinese families with DSH. Whole-exome and Sanger sequencing were performed to detect pathogenic gene mutation in the patients. Bioinformatics tools were used to predict the pathogenicity of the variants.

Results: Four heterozygous ADAR1 variants were identified, including two novel missense variants c.2369G>C (Arg790Pro), and 503C>T (Pro168Leu), and two previously reported variants: c.3232C>T(R1078C), and c.1472C>G (p.S491X). The novel c.503C>T variant was predicted as "deleterious" (score =-2.704) by PROVEAN, and "probably damaging" (score = 1) by PolyPhen2. The other novel variant c.2369G>C was also predicted as "deleterious" (score =-4.167) by PROVEAN, "probably damaging" (score = 1) by PolyPhen2, and "disease-causing" (p = 0.999) by Mutation Taster.

Conclusion: Two novel ADAR1 variants were found in Chinese patients with DSH. This research has expanded the ADAR1 gene database for DSH, enhancing our comprehension of the underlying mechanisms.

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三个中国遗传性对称色素沉着病家族中 ADAR1 基因的两个新变异和两个复发性变异

目的：对称性遗传色素沉着病（Dyschromatosis symmetrica hereditaria，DSH）是一种罕见的常染色体显性遗传色素性皮肤病。DSH的致病基因已被确认为作用于RNA1的腺苷脱氨酶（ADAR1）。本研究旨在确定三个中国DSH家族中ADAR1基因的致病变异：收集了三个中国DSH家族的数据和血液样本。患者和方法：收集三个中国DSH家族的数据和血样，通过全外显子组测序和Sanger测序检测患者的致病基因突变。使用生物信息学工具预测变异基因的致病性：结果：发现了四个ADAR1杂合变异，包括两个新的错义变异c.2369G>C（Arg790Pro）和503C>T（Pro168Leu），以及两个之前报道过的变异：c.3232C>T（R1078C）和c.1472C>G（p.S491X）。新型 c.503C>T 变异被 PROVEAN 预测为 "有害"（得分 =-2.704），被 PolyPhen2 预测为 "可能有害"（得分 = 1）。另一个新型变异 c.2369G>C 也被 PROVEAN 预测为 "有害"（得分 =-4.167），被 PolyPhen2 预测为 "可能有害"（得分 = 1），被 Mutation Taster 预测为 "致病"（p = 0.999）：结论：在中国的DSH患者中发现了两个新的ADAR1变异体。结论：在中国DSH患者中发现了两个新的ADAR1基因变异。这项研究扩大了DSH的ADAR1基因数据库，提高了我们对其潜在机制的理解。

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

Clinical, Cosmetic and Investigational Dermatology Medicine-Dermatology

CiteScore

2.80

自引率

4.30%

发文量

353

审稿时长

16 weeks

期刊介绍： Clinical, Cosmetic and Investigational Dermatology is an international, peer-reviewed, open access journal that focuses on the latest clinical and experimental research in all aspects of skin disease and cosmetic interventions. Normal and pathological processes in skin development and aging, their modification and treatment, as well as basic research into histology of dermal and dermal structures that provide clinical insights and potential treatment options are key topics for the journal. Patient satisfaction, preference, quality of life, compliance, persistence and their role in developing new management options to optimize outcomes for target conditions constitute major areas of interest. The journal is characterized by the rapid reporting of clinical studies, reviews and original research in skin research and skin care. All areas of dermatology will be covered; contributions will be welcomed from all clinicians and basic science researchers globally.