Digenic inheritance in autosomal recessive non-syndromic hearing loss cases carrying GJB2 heterozygote mutations: Assessment of GJB4, GJA1, and GJC3

Kooshavar, Daniz. and Tabatabaiefar, Mohammad Amin. and Farrokhi, Effat. and Abolhasani, Marziyeh. and Noori-Daloii, Mohammad Reza. and Hashemzadeh-Chaleshtori, Morteza. (2013) Digenic inheritance in autosomal recessive non-syndromic hearing loss cases carrying GJB2 heterozygote mutations: Assessment of GJB4, GJA1, and GJC3. INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY, 77 (2). pp. 189-193.

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Abstract

Objective: Autosomal recessive non-syndromic hearing loss (ARNSHL) can be caused by many genes. However, mutations in the GJB2 gene, which encodes the gap-junction (GJ) protein connexin (Cx) 26, constitute a considerable proportion differing among population. Between 10 and 42 percent of patients with recessive GJB2 mutations carry only one mutant allele. Mutations in GJB4, GJA1, and GJC3 encoding Cx30.3, Cx43, and Cx29, respectively, can lead to HL Combination of different connexins in heteromeric and heterotypic GJ assemblies is possible. This study aims to determine whether variations in any of the genes GJB4, GJA1 or GJC3 can be the second mutant allele causing the disease in the digenic mode of inheritance in the studied GJB2 heterozygous cases. Methods: We examined 34 unrelated GJB2 heterozygous ARNSHL subjects from different geographic and ethnic areas in Iran, using polymerase chain reaction (PCR) followed by direct DNA sequencing to identify any sequence variations in these genes. Restriction fragment length polymorphism (RFLP) assays were performed on 400 normal hearing individuals. Results: Sequence analysis of GJB4 showed five heterozygous variations including cA51C>A, c.219C>T, c.507C>G, c.155_158delTCTG and c.542C>T, with only the latter variation not being detected in any of control samples. There were three heterozygous variations including c.758C>T, c.717G>A and c.3*dupA in GJA1 in four cases. We found no variations in GJC3 gene sequence. Conclusion: Our data suggest that GJB4 c.542C>T variant and less likely some variations of GJB4 and GJA1, but not possibly GJC3, can be assigned to ARNSHL in GJB2 heterozygous mutation carriers providing clues of the digenic pattern. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Item Type: Article
Uncontrolled Keywords: Digenic inheritance; Hearing loss; Connexin; GJB2; GJB4; GJA1
Subjects: QU Biochemistry > Cell biology and genetics
WV Otolaryngology
Divisions: Reserach Vice-Chancellar Department > Cellular and Molecular Research Center
Depositing User: zahra bagheri .
Date Deposited: 08 Aug 2017 03:35
Last Modified: 16 May 2018 05:07
URI: http://eprints.skums.ac.ir/id/eprint/2558

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