中国西北地区听力损失患者的突变谱:鉴定 20 种新型变异。

IF 1.5 4区 医学 Q4 GENETICS & HEREDITY
Panpan Ma, Bingbo Zhou, Qichao Kang, Xue Chen, Xinyuan Tian, Ling Hui, Shengju Hao, Huiyan Wu, Chuan Zhang
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引用次数: 0

摘要

背景:听力损失(HL)是人类最常见的感官缺陷,具有很强的遗传异质性。听力损失的基因诊断对于辅助治疗决策、为患者家属提供预后信息和遗传咨询非常重要:方法:我们通过对 15 个热点突变的变异进行筛查,发现并分析了 362 例中国非综合征 HL 患者。随后,40 名患者接受了进一步的全外显子组测序(WES),以确定遗传病因。候选变异通过桑格测序进行了验证。23对携带致病变异或可能携带致病变异的夫妇选择使用桑格测序法进行产前诊断:结果:在 362 例 HL 患者中,102 例通过 22 个耳聋基因中的 52 个不同变体进行了分子诊断。共检测到 41 例(11.33%)双拷贝 GJB2(OMIM # 220290)基因突变,21 例(5.80%)双拷贝 SLC26A4(OMIM # 605646)基因突变。7名患者(1.93%)检测到线粒体基因(OMIM # 561000)变异。15 个耳聋基因中有 20 个是新变异。有两名患者分别检测到 SOX10(OMIM # 602229)、MYO15A(OMIM # 602666)和 WFS1(OMIM # 606201)变异。同时,OSBPL2 (OMIM # 606731)、RRM2B (OMIM # 604712)、OTOG (OMIM # 604487)、STRC (OMIM # 606440)、PCDH15 (OMIM # 605514)、LOXHD1 (OMIM # 613072)、CDH23 (OMIM # 605516)、TMC1 (OMIM # 606706)、CHD7 (OMIM # 608892)、DIAPH3 (OMIM # 614567)、TBC1D24 (OMIM # 613577)、TIMM8A (OMIM # 300356)、PTPRQ (OMIM # 603317)、SALL1 (OMIM # 602218) 和 GSDME (OMIM # 608798) 均在一名患者中检测到。此外,一对夫妇分别患有 CDH23 和 PCDH15 的杂合变异,产前诊断结果显示,胎儿患有 CDH23 和 PCDH15 的双杂合(DH)变异,这种变异极有可能导致 ID/F 型乌谢尔综合征:我们的研究扩大了耳聋基因变异的范围,这将有助于耳聋夫妇的基因诊断、产前诊断和生育指导。此外,在对双聋家庭进行产前诊断时,应注意由两个基因引起的耳聋。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Mutation spectrum of hearing loss patients in Northwest China: Identification of 20 novel variants.

Background: Hearing loss (HL) is the most frequent sensory deficit in humans, with strong genetic heterogeneity. The genetic diagnosis of HL is very important to aid treatment decisions and to provide prognostic information and genetic counselling for the patient's family.

Methods: We detected and analysed 362 Chinese non-syndromic HL patients by screening of variants in 15 hot spot mutations. Subsequently, 40 patients underwent further whole-exome sequencing (WES) to determine genetic aetiology. The candidate variants were verified using Sanger sequencing. Twenty-three carrier couples with pathogenic variants or likely pathogenic variants chose to proceed with prenatal diagnosis using Sanger sequencing.

Results: Among the 362 HL patients, 102 were assigned a molecular diagnosis with 52 different variants in 22 deafness genes. A total of 41 (11.33%) cases with the biallelic GJB2 (OMIM # 220290) gene mutations were detected, and 21 (5.80%) had biallelic SLC26A4 (OMIM # 605646) mutations. Mitochondrial gene (OMIM # 561000) mutations were detected in seven (1.93%) patients. Twenty of the variants in 15 deafness genes were novel. SOX10 (OMIM # 602229), MYO15A (OMIM # 602666) and WFS1 (OMIM # 606201) were each detected in two patients. Meanwhile, OSBPL2 (OMIM # 606731), RRM2B (OMIM # 604712), OTOG (OMIM # 604487), STRC (OMIM # 606440), PCDH15 (OMIM # 605514), LOXHD1 (OMIM # 613072), CDH23 (OMIM # 605516), TMC1 (OMIM # 606706), CHD7 (OMIM # 608892), DIAPH3 (OMIM # 614567), TBC1D24 (OMIM # 613577), TIMM8A (OMIM # 300356), PTPRQ (OMIM # 603317), SALL1 (OMIM # 602218), and GSDME (OMIM # 608798) were each detected in one patient. In addition, as regards one couple with a heterozygous variant of CDH23 and PCDH15, respectively, prenatal diagnosis results suggest that the foetus had double heterozygous (DH) variants of CDH23 and PCDH15, which has a high risk to cause ID/F type Usher syndrome.

Conclusion: Our study expanded the spectrum of deafness gene variation, which will contribute to the genetic diagnosis, prenatal diagnosis and the procreation guidance of deaf couple. In addition, the deafness caused by two genes should be paid attention to in the prenatal diagnosis of families with both deaf patients.

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来源期刊
Molecular Genetics & Genomic Medicine
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.
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