NDLI: The pathological effects of connexin 26 variants related to hearing loss by in silico and in vitro analysis

Content Provider	Springer Nature Link
Author	Kim, Hui Ram Oh, Se Kyung Lee, Eun Shil Choi, Soo Young Roh, Seung Eon Kim, Sang Jeong Tsukihara, Tomitake Lee, Kyu Yup Jeon, Chang Jin Kim, Un Kyung
Copyright Year	2016
Abstract	Gap junctions (GJs) are intercellular channels associated with cell–cell communication. Connexin 26 (Cx26) encoded by the GJB2 gene forms GJs of the inner ear, and mutations of GJB2 cause congenital hearing loss that can be syndromic or non-syndromic. It is difficult to predict pathogenic effects using only genetic analysis. Using ionic and biochemical coupling tests, we evaluated the pathogenic effects of Cx26 variants using computational analyses to predict structural abnormalities. For seven out of ten variants, we predicted the variation would result in a loss of GJ function, whereas the others would completely fail to form GJs. Functional studies demonstrated that, although all variants were able to function normally as hetero-oligomeric GJ channels, six variants (p.E47K, p.E47Q, p.H100L, p.H100Y, p.R127L, and p.M195L) did not function normally as homo-oligomeric GJ channels. Interestingly, GJs composed of the Cx26 variant p.R127H were able to function normally, even as homo-oligomeric GJ channels. This study demonstrates the particular location and property of an amino acid are more important mainly than the domain where they belong in the formation and function of GJ, and will provide information that is useful for the accurate diagnosis of hearing loss.
Starting Page	287
Ending Page	298
Page Count	12
File Format	PDF
ISSN	03406717
Journal	Human Genetics
Volume Number	135
Issue Number	3
e-ISSN	14321203
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2016-01-09
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Human Genetics Molecular Medicine Gene Function Metabolic Diseases
Content Type	Text
Resource Type	Article
Subject	Genetics Genetics (clinical)

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