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Mutations in GJB2 as Major Causes of Autosomal Recessive Non-Syndromic Hearing Loss: First Report of c.299-300delAT Mutation in Kurdish Population of Iran

BACKGROUND AND OBJECTIVES: Autosomal recessive non-syndromic hearing loss (ARNSHL) with genetic origin is common (1/2000 births). ARNSHL can be associated with mutations in gap junction protein beta 2 (GJB2). To this end, this cohort investigation aimed to find the contribution of GJB2 gene mutation...

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Autores principales: Azadegan-Dehkordi, Fatemeh, Bahrami, Tayyebe, Shirzad, Maryam, Karbasi, Gelareh, Yazdanpanahi, Nasrin, Farrokhi, Effat, Koohiyan, Mahbobeh, Tabatabaiefar, Mohammad Amin, Hashemzadeh-Chaleshtori, Morteza
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Audiological Society and Korean Otological Society 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348308/
https://www.ncbi.nlm.nih.gov/pubmed/30518198
http://dx.doi.org/10.7874/jao.2018.00185
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author Azadegan-Dehkordi, Fatemeh
Bahrami, Tayyebe
Shirzad, Maryam
Karbasi, Gelareh
Yazdanpanahi, Nasrin
Farrokhi, Effat
Koohiyan, Mahbobeh
Tabatabaiefar, Mohammad Amin
Hashemzadeh-Chaleshtori, Morteza
author_facet Azadegan-Dehkordi, Fatemeh
Bahrami, Tayyebe
Shirzad, Maryam
Karbasi, Gelareh
Yazdanpanahi, Nasrin
Farrokhi, Effat
Koohiyan, Mahbobeh
Tabatabaiefar, Mohammad Amin
Hashemzadeh-Chaleshtori, Morteza
author_sort Azadegan-Dehkordi, Fatemeh
collection PubMed
description BACKGROUND AND OBJECTIVES: Autosomal recessive non-syndromic hearing loss (ARNSHL) with genetic origin is common (1/2000 births). ARNSHL can be associated with mutations in gap junction protein beta 2 (GJB2). To this end, this cohort investigation aimed to find the contribution of GJB2 gene mutations with the genotype-phenotype correlations in 45 ARNSHL cases in the Kurdish population. SUBJECTS AND METHODS: Genomic DNA was extracted from a total of 45 ARNSHL families. The linkage analysis with 3 short tandem repeat markers linked to GJB2 was performed on 45 ARNSHL families. Only 9 of these families were linked to the DFNB1 locus. All the 45 families who took part were sequenced for confirmation linkage analysis (to perform a large project). RESULTS: A total of three different mutations were determined. Two of which [c.35delG and c.-23+1G>A (IVS1+1G>A)] were previously reported but (c.299-300delAT) mutation was novel in the Kurdish population. The homozygous pathogenic mutations of GJB2 gene was observed in nine out of the 45 families (20%), also heterozygous genotype (c.35delG/N)+(c.-23+1G>A/c.-23+1G>A) were observed in 4/45 families (8.8%). The degree of hearing loss (HL) in patients with other mutations was less severe than patients with c.35delG homozygous mutation (p<0.001). CONCLUSIONS: Our data suggest that GJB2 mutations constitute 20% of the etiology of ARNSHL in Iran; moreover, the c.35delG mutation is the most common HL cause in the Kurdish population. Therefore, these mutations should be included in the molecular testing of HL in this population.
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spelling pubmed-63483082019-02-05 Mutations in GJB2 as Major Causes of Autosomal Recessive Non-Syndromic Hearing Loss: First Report of c.299-300delAT Mutation in Kurdish Population of Iran Azadegan-Dehkordi, Fatemeh Bahrami, Tayyebe Shirzad, Maryam Karbasi, Gelareh Yazdanpanahi, Nasrin Farrokhi, Effat Koohiyan, Mahbobeh Tabatabaiefar, Mohammad Amin Hashemzadeh-Chaleshtori, Morteza J Audiol Otol Original Article BACKGROUND AND OBJECTIVES: Autosomal recessive non-syndromic hearing loss (ARNSHL) with genetic origin is common (1/2000 births). ARNSHL can be associated with mutations in gap junction protein beta 2 (GJB2). To this end, this cohort investigation aimed to find the contribution of GJB2 gene mutations with the genotype-phenotype correlations in 45 ARNSHL cases in the Kurdish population. SUBJECTS AND METHODS: Genomic DNA was extracted from a total of 45 ARNSHL families. The linkage analysis with 3 short tandem repeat markers linked to GJB2 was performed on 45 ARNSHL families. Only 9 of these families were linked to the DFNB1 locus. All the 45 families who took part were sequenced for confirmation linkage analysis (to perform a large project). RESULTS: A total of three different mutations were determined. Two of which [c.35delG and c.-23+1G>A (IVS1+1G>A)] were previously reported but (c.299-300delAT) mutation was novel in the Kurdish population. The homozygous pathogenic mutations of GJB2 gene was observed in nine out of the 45 families (20%), also heterozygous genotype (c.35delG/N)+(c.-23+1G>A/c.-23+1G>A) were observed in 4/45 families (8.8%). The degree of hearing loss (HL) in patients with other mutations was less severe than patients with c.35delG homozygous mutation (p<0.001). CONCLUSIONS: Our data suggest that GJB2 mutations constitute 20% of the etiology of ARNSHL in Iran; moreover, the c.35delG mutation is the most common HL cause in the Kurdish population. Therefore, these mutations should be included in the molecular testing of HL in this population. The Korean Audiological Society and Korean Otological Society 2019-01 2018-12-07 /pmc/articles/PMC6348308/ /pubmed/30518198 http://dx.doi.org/10.7874/jao.2018.00185 Text en Copyright © 2019 The Korean Audiological Society and Korean Otological Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Azadegan-Dehkordi, Fatemeh
Bahrami, Tayyebe
Shirzad, Maryam
Karbasi, Gelareh
Yazdanpanahi, Nasrin
Farrokhi, Effat
Koohiyan, Mahbobeh
Tabatabaiefar, Mohammad Amin
Hashemzadeh-Chaleshtori, Morteza
Mutations in GJB2 as Major Causes of Autosomal Recessive Non-Syndromic Hearing Loss: First Report of c.299-300delAT Mutation in Kurdish Population of Iran
title Mutations in GJB2 as Major Causes of Autosomal Recessive Non-Syndromic Hearing Loss: First Report of c.299-300delAT Mutation in Kurdish Population of Iran
title_full Mutations in GJB2 as Major Causes of Autosomal Recessive Non-Syndromic Hearing Loss: First Report of c.299-300delAT Mutation in Kurdish Population of Iran
title_fullStr Mutations in GJB2 as Major Causes of Autosomal Recessive Non-Syndromic Hearing Loss: First Report of c.299-300delAT Mutation in Kurdish Population of Iran
title_full_unstemmed Mutations in GJB2 as Major Causes of Autosomal Recessive Non-Syndromic Hearing Loss: First Report of c.299-300delAT Mutation in Kurdish Population of Iran
title_short Mutations in GJB2 as Major Causes of Autosomal Recessive Non-Syndromic Hearing Loss: First Report of c.299-300delAT Mutation in Kurdish Population of Iran
title_sort mutations in gjb2 as major causes of autosomal recessive non-syndromic hearing loss: first report of c.299-300delat mutation in kurdish population of iran
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348308/
https://www.ncbi.nlm.nih.gov/pubmed/30518198
http://dx.doi.org/10.7874/jao.2018.00185
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