Frequency of GJB2 mutations in families with autosomal recessive non-syndromic hearing loss in Khuzestan province

Background: Autosomal recessive non-syndromic hearing loss (ARNSHL), one of the global public health concerns, is marked by a high degree of genetic heterogeneity. The role of GJB2, as the most common cause of ARNSHL, is only <20% in the Iranian population. Here, we aimed to determine the relative contribution of several apparently most common loci in a cohort of ARNSHL Iranian families that were negative for the GJB2 mutations. Methods: Totally, 80 Iranian ARNSHL families with 3 or more affected individuals from Isfahan and Hamedan provinces, Iran were enrolled in 2017. After excluding mutations in the GJB2 gene via Sanger sequencing, 60 negative samples (30 families from each province) were analyzed using homozygosity mapping for 10 ARNSHL loci. Results: Fourteen families were found to be linked to five different known loci, including DFNB4 (5 families), DFNB2 (3 families), DFNB7/11 (1 family), DFNB9 (2 families) and DFNB3 (3 families). Conclusion: Despite the high heterogeneity of ARNSHL, the genetic causes were determined in 23.5% of the studied families using homozygosity mapping. This data gives an overview of the ARNSHL etiology in the center and west of Iran, used to establish a diagnostic gene panel including most common loci for hearing loss diagnostics.

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Genetic linkage analysis of DFNB22 in families with autosomal recessive non-syndromic hearing loss in Khuzestan province

Journal of Shahrekord University of Medical Sciences ◽

10.34172/jsums.2019.35 ◽

2019 ◽

Vol 21 (5) ◽

pp. 200-203

Author(s):

Ladan Sadeghian ◽

Mohammad Amin Tabatabaiefar ◽

Morteza Hashemzadeh Chaleshtori

Keyword(s):

Hearing Loss ◽

Linkage Analysis ◽

Autosomal Recessive ◽

Polyacrylamide Gel Electrophoresis ◽

Genetic Linkage Analysis ◽

Haplotype Reconstruction ◽

Limited Information ◽

Khuzestan Province ◽

Syndromic Hearing Loss

Background and aims: Hearing loss (HL) is the most common sensorineural disorder affecting 1 in 1000 newborns. Autosomal recessive non-syndromic hearing loss (ARNSHL), which is the most common cause of severe HL, is caused by mutations in more than 80 loci. The OTOA gene located on DFNB22 is a rare cause of the disease and the gene studied less in Iranian ARNSHL families. Hence, limited information is available on the frequency and type of OTOA mutations in different populations. In this study, we investigated the role of DFNB22 locus in ARNSHL patients in Khuzestan province, Iran. Materials and Methods: In this descriptive-experimental study, 23 large families with pre-lingual ARNSHL from Khuzestan province were enrolled. Mutations in GJB2 were excluded by DNA sequencing followed by linkage analysis. Homozygosity mapping of DFNB22 was conducted using 6 short tandem repeat polymorphic markers via touch-down PCR and polyacrylamide gel electrophoresis. Homozygosityby-descent was identified by calculating two-point and multi-point LOD score and haplotype reconstruction. Results: Families were negative for GJB2 mutations. Genotyping the STRP markers, haplotype reconstruction, and two-point and multiplepoint LOD scores did not show homozygosity-by-descent in any of the pedigrees. Conclusion: Our findings suggest that OTOA mutations might not contribute significantly to the molecular pathophysiology of ARNSHL in Khuzestan province. However, extending the sample size can illuminate the role of this gene in Khuzestan province.

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High prevalence of theW24X mutation in the gene encoding connexin-26 (GJB2) in Spanish Romani (gypsies) with autosomal recessive non-syndromic hearing loss

American Journal of Medical Genetics Part A ◽

10.1002/ajmg.a.30884 ◽

2005 ◽

Vol 137A (3) ◽

pp. 255-258 ◽

Cited By ~ 52

Author(s):

Araceli Álvarez ◽

Ignacio del Castillo ◽

Manuela Villamar ◽

Luis A. Aguirre ◽

Anna González-Neira ◽

...

Keyword(s):

Hearing Loss ◽

Autosomal Recessive ◽

Connexin 26 ◽

Gene Encoding ◽

High Prevalence ◽

Syndromic Hearing Loss

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Decreased disulphide/thiol ratio in patients with autosomal recessive non-syndromic hearing loss

International Journal of Pediatric Otorhinolaryngology ◽

10.1016/j.ijporl.2018.07.014 ◽

2018 ◽

Vol 112 ◽

pp. 188-192

Author(s):

Burhan Balta ◽

Ramazan Gundogdu ◽

Murat Erdogan ◽

Murat Alisik ◽

Aslihan Kiraz ◽

...

Keyword(s):

Hearing Loss ◽

Autosomal Recessive ◽

Syndromic Hearing Loss

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An update of common autosomal recessive non-syndromic hearing loss genes in Iranian population

International Journal of Pediatric Otorhinolaryngology ◽

10.1016/j.ijporl.2017.04.007 ◽

2017 ◽

Vol 97 ◽

pp. 113-126 ◽

Cited By ~ 13

Author(s):

Tohid Ghasemnejad ◽

Mahmoud Shekari Khaniani ◽

Fatemeh Zarei ◽

Mina Farbodnia ◽

Sima Mansoori Derakhshan

Keyword(s):

Hearing Loss ◽

Autosomal Recessive ◽

Iranian Population ◽

Syndromic Hearing Loss

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Whole Exome Sequencing of Six Chinese Families With Hereditary Non-Syndromic Hearing Loss: A Genetic Etiology Study

10.21203/rs.3.rs-132767/v1 ◽

2020 ◽

Author(s):

Pengfei Liang ◽

Fengping Chen ◽

Shujuan Wang ◽

Qiong Li ◽

Wei Li ◽

...

Keyword(s):

Hearing Loss ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Sanger Sequencing ◽

Large Scale ◽

Autosomal Recessive ◽

Autosomal Recessive Inheritance ◽

Chinese Families ◽

Whole Exome ◽

Syndromic Hearing Loss

Abstract Background: Hereditary non-syndromic hearing loss (NSHL) has a high genetic heterogeneity with >152 genes identified as associated molecular causes. The present study aimed to detect the possible damaging variants of the deaf probands from six unrelated Chinese families.Methods: After excluding the mutations in the most common genes, GJB2 and SLC26A4, 12 probands with prelingual deafness and autosomal recessive inheritance were evaluated by whole-exome sequencing (WES). All the candidate variants were verified by Sanger sequencing in all patients and their parents.Results: Biallelic mutations were identified in all deaf patients. Among these six families, 10 potentially causative mutations, including 3 reported and 7 novel mutations, in 3 different deafness-associated autosomal recessive (DFNB) genes (MYO15A, COL11A2, and CDH23) were identified. The mutations in MYO15A were frequent with 7/10 candidate variants. Sanger sequencing confirmed that these mutations segregated with the hearing loss of each family.Conclusions: Next-generation sequencing (NGS) approach becomes more cost-effective and efficient when analyzing large-scale genes compared to the conventional polymerase chain reaction-based Sanger sequencing, which is often used to screen common deafness-related genes. The current findings further extend the mutation spectrum of hearing loss in the Chinese population, which has a positive significance for genetic counseling.

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