Finding mutation within non-coding region of GJB2 reveals its importance in genetic testing of Hearing Loss in Iranian population

Kashef, Atie; Nikzat, Nooshin; Bazzazadegan, Niloofar; Fattahi, Zohreh; Sabbagh-Kermani, Farahnaz; Taghdiri, Maryam; Azadeh, Batool; Mojahedi, Faezeh; Khoshaeen, Atefeh; Habibi, Haleh; Najmabadi, Hossein; Kahrizi, Kimia

doi:10.1016/j.ijporl.2014.11.024

Cited by 3 publications

(7 citation statements)

References 18 publications

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“…A relatively large proportion of deaf individuals carrying only one pathogenic recessive GJB2 variant has been reported in many previous studies [6,7,41,53,54,55,56,57,58,59,60,61]. Two main assumptions have been made to resolve this issue: (1) HL of such patients could be caused by an uncertain impact of the GJB2 gene (the presence of yet undetected other pathogenic GJB2 variants or variable penetrance of pathogenic GJB2 variant due to any modulating factors); (2) these patients are only the coincidental carriers of one pathogenic GJB2 allele and other factors (other genes or environmental impacts) cause their HL.…”

Section: Resultsmentioning

confidence: 99%

“…A large number of deaf individuals with a single recessive GJB2 pathogenic allele was detected in different studies, which complicates the molecular diagnosis for their HL [6,7,41,53,54,55,56,57,58,59,60,61,72]. These findings may partly be explained by the fact that only the GJB2 coding region (exon 2) was tested in some older studies; therefore, potential pathogenic variations in the GJB2 non-coding or regulatory regions could be missed.…”

Section: Discussionmentioning

confidence: 99%

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Unique Mutational Spectrum of the GJB2 Gene and Its Pathogenic Contribution to Deafness in Tuvinians (Southern Siberia, Russia): A High Prevalence of Rare Variant c.516G>C (p.Trp172Cys)

Posukh

Zytsar

Бады-Хоо

et al. 2019

Genes

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Mutations in the GJB2 gene are the main cause for nonsyndromic autosomal recessive deafness 1A (DFNB1A) in many populations. GJB2 mutational spectrum and pathogenic contribution are widely varying in different populations. Significant efforts have been made worldwide to define DFNB1A molecular epidemiology, but this issue still remains open for some populations. The main aim of study is to estimate the DFNB1A prevalence and GJB2 mutational spectrum in Tuvinians—an indigenous population of the Tyva Republic (Southern Siberia, Russia). Sanger sequencing was applied to analysis of coding (exon 2) and non-coding regions of GJB2 in a cohort of Tuvinian patients with hearing impairments (n = 220) and ethnically matched controls (n = 157). Diagnosis of DFNB1A was established for 22.3% patients (28.8% of familial vs 18.6% of sporadic cases). Our results support that patients with monoallelic GJB2 mutations (8.2%) are coincidental carriers. Recessive mutations p.Trp172Cys, c.-23+1G>A, c.235delC, c.299_300delAT, p.Val37Ile and several benign variants were found in examined patients. A striking finding was a high prevalence of rare variant p.Trp172Cys (c.516G>C) in Tuvinians accounting for 62.9% of all mutant GJB2 alleles and a carrier frequency of 3.8% in controls. All obtained data provide important targeted information for genetic counseling of affected Tuvinian families and enrich current information on variability of GJB2 worldwide.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Unique Mutational Spectrum of the GJB2 Gene and Its Pathogenic Contribution to Deafness in Tuvinians (Southern Siberia, Russia): A High Prevalence of Rare Variant c.516G>C (p.Trp172Cys)

Posukh

Zytsar

Бады-Хоо

et al. 2019

Genes

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“…In some cases, mutations in GJB6 (homozygous mutations along with heterozygous mutations in GJB2) (DEL CASTILLO, I. et al, 2003;ERBE et al, 2004;PANDYA et al, 2003) or homozygous mutations in the first exon of GJB2 can cause HL (DENOYELLE et al, 1999;KASHEF et al, 2015;MANI et al, 2009). Therefore, in the remaining studied families (44 families) with or without heterozygous mutations in GJB2, the DFNB1 locus linkage analysis was conducted for the related markers and no linkage was observed.…”

Section: Resultsmentioning

confidence: 99%

“…This further shows the necessity of studying the main loci contributing to HL and determining the contribution of each of them in causing this disease in Khuzestan province. It should be noted that most of the studies in Iran have been conducted on the combination of the population of several provinces (BABANEJAD et al, 2012;BAZAZZADEGAN et al, 2012;KASHEF et al, 2015;TABATABAIEFAR et al, 2011).…”

Section: Resultsmentioning

confidence: 99%

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

Tahmasebi¹,

Hashemzadeh²,

Abdollahnejad³

et al. 2018

Genetika

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Hearing loss is caused both by genetic and environmental factors. In this sense, more than half of the cases are genetic. Hereditary hearing loss is divided into syndromic and nonsyndromic cases. Main pattern of inheritance (80%) in non-syndromic cases is autosomal recessive, which is known as autosomal recessive non-syndromic hearing loss (ARNSHL). Although the disease is very genetically heterogeneous, the GJB2 gene has 838

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A Novel Pathologic Variant in OTOF in an Iranian Family Segregating Hereditary Hearing Loss

Tabatabaiefar

Pourreza

Tahmasebi

et al. 2018

Otolaryngol.--head neck surg.

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Objective Hearing loss (HL) is the most common sensory-neural defect and the most heterogeneous trait in humans, with the involvement of >100 genes, which make a molecular diagnosis problematic. Next-generation sequencing (NGS) is a new strategy that can overcome this problem. Study Design Descriptive experimental study. Setting Diagnostic laboratory. Subjects and Methods A comprehensive family history was obtained, and clinical evaluations and pedigree analysis were performed in a family with multiple individuals with HL. As the first tier, GJB2 was sequenced, and genetic linkage analysis of DFNB1A/B was performed to rule out the most common cause of the disease. Targeted NGS was used to unravel the molecular etiology of the disease in the HL-associated genes in the proband. Two homozygous variants remained in OTOF after proper filtration. Cosegregation and in silico analysis were done. Preimplantation genetic diagnosis (PGD) was accomplished via linkage analysis and direct sequencing of the pathogenic variant. Results Clinical evaluations suggested autosomal recessive nonsyndromic HL. Two homozygous variants, c.367G>A (p.Gly123Ser) and c.1392+1G>A, were identified in cis status. c.1392+1G>A met the criteria for being pathogenic according to the variant interpretation guideline of the American College of Medical Genetics and Genomics. PGD was successfully performed to prevent the recurrence of the disease in the related family. Conclusion A novel OTOF mutation causing HL was identified. Here, we report the effectiveness of the combined application of targeted NGS and PGD in diagnosis and prevention of hereditary HL.

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Finding mutation within non-coding region of GJB2 reveals its importance in genetic testing of Hearing Loss in Iranian population

Cited by 3 publications

References 18 publications

Unique Mutational Spectrum of the GJB2 Gene and Its Pathogenic Contribution to Deafness in Tuvinians (Southern Siberia, Russia): A High Prevalence of Rare Variant c.516G>C (p.Trp172Cys)

Unique Mutational Spectrum of the GJB2 Gene and Its Pathogenic Contribution to Deafness in Tuvinians (Southern Siberia, Russia): A High Prevalence of Rare Variant c.516G>C (p.Trp172Cys)

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

A Novel Pathologic Variant in OTOF in an Iranian Family Segregating Hereditary Hearing Loss

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