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Genetic Linkage Analysis of DFNB4, DFNB28, DFNB93 Loci in Autosomal Recessive Non-syndromic Hearing Loss: Evidence for Digenic Inheritance in GJB2 and GJB3 Mutations

BACKGROUND: Autosomal recessive non-syndromic hearing loss (ARNSHL) a most frequent hereditary type of hearing impairment, exhibit tremendous genetic heterogeneity. We aimed to determine the contribution of three common DFNB loci (DFNB4, DFNB28, and DFNB93), and mutation analysis of Gap Junction Bet...

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Autores principales: NASERI, Marzieh, AKBARZADEHLALEH, Masoud, MASOUDI, Marjan, AHANGARI, Najmeh, POURSADEGH ZONOUZI, Ali Akbar, POURSADEGH ZONOUZI, Ahmad, SHAMS, Leila, NEJATIZADEH, Azim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Tehran University of Medical Sciences 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756606/
https://www.ncbi.nlm.nih.gov/pubmed/29318123
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author NASERI, Marzieh
AKBARZADEHLALEH, Masoud
MASOUDI, Marjan
AHANGARI, Najmeh
POURSADEGH ZONOUZI, Ali Akbar
POURSADEGH ZONOUZI, Ahmad
SHAMS, Leila
NEJATIZADEH, Azim
author_facet NASERI, Marzieh
AKBARZADEHLALEH, Masoud
MASOUDI, Marjan
AHANGARI, Najmeh
POURSADEGH ZONOUZI, Ali Akbar
POURSADEGH ZONOUZI, Ahmad
SHAMS, Leila
NEJATIZADEH, Azim
author_sort NASERI, Marzieh
collection PubMed
description BACKGROUND: Autosomal recessive non-syndromic hearing loss (ARNSHL) a most frequent hereditary type of hearing impairment, exhibit tremendous genetic heterogeneity. We aimed to determine the contribution of three common DFNB loci (DFNB4, DFNB28, and DFNB93), and mutation analysis of Gap Junction Beta-2 gene (GJB2) and GJB3 genes in ARNSHL subjects in southern Iran. METHODS: Thirty-six large ARNSHL pedigrees (167 individuals) with at least two affected subjects (72 patients) were included in this descriptive study from Hormozgan Province of Iran, during 2014 – 2015. The variation of GJB2 and GJB3 genes were screened using direct sequencing method. The negative samples for GJB2 and GJB3 genes mutations were analyzed for the linkage to DFNB4, DFNB28, and DFNB93 loci by genotyping the corresponding short tandem repeat (STR) markers using polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE) methods. RESULTS: DNA sequencing of GJB2 were identified heterozygous mutation (964 C/T) in 13.88% of the studied families. Three missense mutations (788G/A, 284C/T and 973G/C) were also detected in coding region of the GJB3 gene. The 284C/T mutation in the GJB3 occurs in compound heterozygosity along with the 964T/C mutation in the GJB2 in one family. Finally, we found no evidence of linkage to either of DFNB4, DFNB93 and DFNB28 loci. CONCLUSION: Highlighting the hypothesis that a genetic interaction between GJB2 and GJB3 genes could be lead to ARNSHL, however, no evidence of linkage to the DFNB loci was found. 284C/T variant in GJB3 gene might be pathogenic when accompanied by variant in GJB2 in a digenic pattern. However, further large-scale familial and functional studies are required to challenge this hypothesis.
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spelling pubmed-57566062018-01-09 Genetic Linkage Analysis of DFNB4, DFNB28, DFNB93 Loci in Autosomal Recessive Non-syndromic Hearing Loss: Evidence for Digenic Inheritance in GJB2 and GJB3 Mutations NASERI, Marzieh AKBARZADEHLALEH, Masoud MASOUDI, Marjan AHANGARI, Najmeh POURSADEGH ZONOUZI, Ali Akbar POURSADEGH ZONOUZI, Ahmad SHAMS, Leila NEJATIZADEH, Azim Iran J Public Health Original Article BACKGROUND: Autosomal recessive non-syndromic hearing loss (ARNSHL) a most frequent hereditary type of hearing impairment, exhibit tremendous genetic heterogeneity. We aimed to determine the contribution of three common DFNB loci (DFNB4, DFNB28, and DFNB93), and mutation analysis of Gap Junction Beta-2 gene (GJB2) and GJB3 genes in ARNSHL subjects in southern Iran. METHODS: Thirty-six large ARNSHL pedigrees (167 individuals) with at least two affected subjects (72 patients) were included in this descriptive study from Hormozgan Province of Iran, during 2014 – 2015. The variation of GJB2 and GJB3 genes were screened using direct sequencing method. The negative samples for GJB2 and GJB3 genes mutations were analyzed for the linkage to DFNB4, DFNB28, and DFNB93 loci by genotyping the corresponding short tandem repeat (STR) markers using polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis (PAGE) methods. RESULTS: DNA sequencing of GJB2 were identified heterozygous mutation (964 C/T) in 13.88% of the studied families. Three missense mutations (788G/A, 284C/T and 973G/C) were also detected in coding region of the GJB3 gene. The 284C/T mutation in the GJB3 occurs in compound heterozygosity along with the 964T/C mutation in the GJB2 in one family. Finally, we found no evidence of linkage to either of DFNB4, DFNB93 and DFNB28 loci. CONCLUSION: Highlighting the hypothesis that a genetic interaction between GJB2 and GJB3 genes could be lead to ARNSHL, however, no evidence of linkage to the DFNB loci was found. 284C/T variant in GJB3 gene might be pathogenic when accompanied by variant in GJB2 in a digenic pattern. However, further large-scale familial and functional studies are required to challenge this hypothesis. Tehran University of Medical Sciences 2018-01 /pmc/articles/PMC5756606/ /pubmed/29318123 Text en Copyright© Iranian Public Health Association & Tehran University of Medical Sciences http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
NASERI, Marzieh
AKBARZADEHLALEH, Masoud
MASOUDI, Marjan
AHANGARI, Najmeh
POURSADEGH ZONOUZI, Ali Akbar
POURSADEGH ZONOUZI, Ahmad
SHAMS, Leila
NEJATIZADEH, Azim
Genetic Linkage Analysis of DFNB4, DFNB28, DFNB93 Loci in Autosomal Recessive Non-syndromic Hearing Loss: Evidence for Digenic Inheritance in GJB2 and GJB3 Mutations
title Genetic Linkage Analysis of DFNB4, DFNB28, DFNB93 Loci in Autosomal Recessive Non-syndromic Hearing Loss: Evidence for Digenic Inheritance in GJB2 and GJB3 Mutations
title_full Genetic Linkage Analysis of DFNB4, DFNB28, DFNB93 Loci in Autosomal Recessive Non-syndromic Hearing Loss: Evidence for Digenic Inheritance in GJB2 and GJB3 Mutations
title_fullStr Genetic Linkage Analysis of DFNB4, DFNB28, DFNB93 Loci in Autosomal Recessive Non-syndromic Hearing Loss: Evidence for Digenic Inheritance in GJB2 and GJB3 Mutations
title_full_unstemmed Genetic Linkage Analysis of DFNB4, DFNB28, DFNB93 Loci in Autosomal Recessive Non-syndromic Hearing Loss: Evidence for Digenic Inheritance in GJB2 and GJB3 Mutations
title_short Genetic Linkage Analysis of DFNB4, DFNB28, DFNB93 Loci in Autosomal Recessive Non-syndromic Hearing Loss: Evidence for Digenic Inheritance in GJB2 and GJB3 Mutations
title_sort genetic linkage analysis of dfnb4, dfnb28, dfnb93 loci in autosomal recessive non-syndromic hearing loss: evidence for digenic inheritance in gjb2 and gjb3 mutations
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5756606/
https://www.ncbi.nlm.nih.gov/pubmed/29318123
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