The pathological effects of connexin 26 variants related to hearing loss by in silico and in vitro analysis
| العنوان: | The pathological effects of connexin 26 variants related to hearing loss by in silico and in vitro analysis |
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| المؤلفون: | Eun Shil Lee, Un Kyung Kim, Chang-Jin Jeon, Seung Eon Roh, Kyu Yup Lee, Se Kyung Oh, Hui Ram Kim, Tomitake Tsukihara, Soo Young Choi, Sang Jeong Kim |
| المصدر: | Human Genetics. 135:287-298 |
| بيانات النشر: | Springer Science and Business Media LLC, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Protein Conformation, Hearing loss, In silico, Connexin, Biology, Transfection, Congenital hearing loss, medicine.disease_cause, Connexins, 03 medical and health sciences, 0302 clinical medicine, otorhinolaryngologic diseases, Genetics, medicine, Humans, Inner ear, Cloning, Molecular, Hearing Loss, Genetics (clinical), Regulation of gene expression, Mutation, Gap Junctions, Genetic Variation, Connexin 26, 030104 developmental biology, medicine.anatomical_structure, Gene Expression Regulation, medicine.symptom, 030217 neurology & neurosurgery, Function (biology), HeLa Cells |
| الوصف: | 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. |
| تدمد: | 1432-1203 0340-6717 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ace6f3ff0b7daef17c1cb9215f6d71ab https://doi.org/10.1007/s00439-015-1625-7 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....ace6f3ff0b7daef17c1cb9215f6d71ab |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 14321203 03406717 |
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