4.5 Article

Rare coding variants involving MYO7A and other genes encoding stereocilia link proteins in familial meniere disease

期刊

HEARING RESEARCH
卷 409, 期 -, 页码 -

出版社

ELSEVIER
DOI: 10.1016/j.heares.2021.108329

关键词

Genomics; Hearing loss; Inner ear; Meniere's disease; Vestibular disorders

资金

  1. Swiss Schmieder-Bohrisch Foundation [H2020-SC1-2019-848261]
  2. ASMES (Spanish Meniere Syndrome Association)
  3. Swiss National Science Foundation (SNSF)
  4. University of Zurich, Switzerland
  5. Universidad de Granada/CBUA

向作者/读者索取更多资源

Rare variants in the MYO7A gene were found to be associated with familial Meniere's disease, with co-segregation of variants in other genes like CDH23, PCDH15, or ADGRV1. These genes may affect the structure of hair cell stereocilia in familial MD.
The MYO7A gene encodes a motor protein with a key role in the organization of stereocilia in auditory and vestibular hair cells. Rare variants in the MYO7A (myosin VIIA) gene may cause autosomal dominant (AD) or autosomal recessive (AR) sensorineural hearing loss (SNHL) accompanied by vestibular dysfunc-tion or retinitis pigmentosa (Usher syndrome type 1B). Familial Meniere's disease (MD) is a rare inner ear syndrome mainly characterized by low-frequency sensorineural hearing loss and episodic vertigo as-sociated with tinnitus. Familial aggregation has been found in 6-8% of sporadic cases, and most of the reported genes were involved in single families. Thus, this study aimed to search for relevant genes not previously linked to familial MD. Through exome sequencing and segregation analysis in 62 MD families, we have found a total of 1 novel and 8 rare heterozygous variants in the MYO7A gene in 9 non-related families. Carriers of rare variants in MYO7A showed autosomal dominant or autosomal recessive SNHL in familial MD. Additionally, some novel and rare variants in other genes involved in the organization of the stereocilia links such as CDH23, PCDH15 or ADGRV1 co-segregated in the same patients. Our find-ings reveal a co-segregation of rare variants in the MYO7A gene and other structural myosin VIIA binding proteins involved in the tip and ankle links of the hair cell stereocilia. We suggest that recessive digenic inheritance involving these genes could affect the ultrastructure of the stereocilia links in familial MD. (c) 2021 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据