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携带GJB2基因c.235delC纯合突变患者的语后聋和/或轻度听力损失的表型异质性

Phenotypic Heterogeneity of Post-lingual and/or Milder Hearing Loss for the Patients With the GJB2 c.235delC Homozygous Mutation.

作者信息

Wang Hongyang, Gao Yun, Guan Jing, Lan Lan, Yang Ju, Xiong Wenping, Zhao Cui, Xie Linyi, Yu Lan, Wang Dayong, Wang Qiuju

机构信息

College of Otolaryngology, Head and Neck Surgery, Chinese People's Liberation Army (PLA) Institute of Otolaryngology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.

National Clinical Research Center for Otolaryngologic Diseases, Beijing, China.

出版信息

Front Cell Dev Biol. 2021 Feb 26;9:647240. doi: 10.3389/fcell.2021.647240. eCollection 2021.

DOI:10.3389/fcell.2021.647240
PMID:33718389
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7953049/
Abstract

OBJECTIVE

To report the phenotypic heterogeneity of c.235delC homozygotes associated with post-lingual and/or milder hearing loss, and explore the possible mechanism of these unconditional phenotypes.

METHODS

Mutation screening of was performed on all ascertained members from Family 1006983 and three sporadic patients by polymerase chain reaction (PCR) amplification and Sanger sequencing. Next generation sequencing (NGS) was successively performed on some of the affected members and normal controls from Family 1006983 to explore additional possible genetic codes. Reverse transcriptase-quantitative PCR was conducted to test the expression of Connexin30.

RESULTS

We identified a Chinese autosomal recessive hearing loss family with the c.235delC homozygous mutation, affected members from which had post-lingual moderate to profound hearing impairment, and three sporadic patients with post-lingual moderate hearing impairment, instead of congenital profound hearing loss. NGS showed no other particular variants. Overexpression of Connexin30 in some of these cases was verified.

CONCLUSION

Post-lingual and/or moderate hearing impairment phenotypes of c.235delC homozygotes are not the most common phenotype, revealing the heterogeneity of pathogenic mutations. To determine the possible mechanism that rescues part of the hearing or postpones onset age of these cases, more cases are required to confirm both Connexin30 overexpression and the existence of modifier genes.

摘要

目的

报告与语后和/或较轻听力损失相关的c.235delC纯合子的表型异质性，并探讨这些非典型表型的可能机制。

方法

通过聚合酶链反应（PCR）扩增和桑格测序对1006983家系的所有确诊成员和3例散发患者进行突变筛查。对1006983家系的部分受累成员和正常对照进行二代测序（NGS），以探索其他可能的遗传密码。进行逆转录定量PCR检测连接蛋白30的表达。

结果

我们鉴定了一个携带c.235delC纯合突变的中国常染色体隐性遗传性听力损失家系，该家系的受累成员有语后中度至重度听力障碍，以及3例语后中度听力障碍的散发患者，而非先天性重度听力损失。NGS未显示其他特殊变异。证实了其中一些病例中连接蛋白30的过表达。

结论

c.235delC纯合子的语后和/或中度听力障碍表型并非最常见的表型，揭示了致病突变的异质性。为了确定挽救部分听力或推迟这些病例发病年龄的可能机制，需要更多病例来证实连接蛋白30的过表达和修饰基因的存在。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8bd/7953049/5add53b80237/fcell-09-647240-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8bd/7953049/d9c3b9ce414e/fcell-09-647240-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8bd/7953049/cc1dab1ed450/fcell-09-647240-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8bd/7953049/7caaba4ea165/fcell-09-647240-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8bd/7953049/5add53b80237/fcell-09-647240-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8bd/7953049/d9c3b9ce414e/fcell-09-647240-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8bd/7953049/cc1dab1ed450/fcell-09-647240-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8bd/7953049/7caaba4ea165/fcell-09-647240-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8bd/7953049/5add53b80237/fcell-09-647240-g004.jpg

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