Rare compound heterozygosity involving dominant and recessive mutations of GJB2 gene in an assortative mating hearing impaired Indian family

Introduction: Sequence variants in the GJB2 gene account for up to 50% of cases of non-syndromic sensorineural hearing loss in the Caucasian population. In this study, we report the frequency of the less common variants of the GJB2 gene in a Portuguese sample and compare these frequencies with those of a group of hearing-impaired patients.Material and Methods: In order to select the less common GJB2 variants, 147 hearing-impaired patients followed in Centro Hospitalar Universitário de São João were evaluated. Afterwards, the presence of those variants was tested in 360 individuals from Generation 21.Results: The patient assessment enabled the selection of 11 GJB2 variants. Of those, 10 were investigated in Generation 21 participants, with only four being detected, in heterozygosity: p.Phe83Leu, p.Arg127His, p.Val153Ile and p.Asn206Ser, with the allelic frequencies (95% confidence interval) of 0.14% (0.01% - 0.87%), 0.28% (0.01% - 1.08%), 0.97% (0.43% - 2.04%) and 0.14% (0.01% - 0.88%), respectively. Two variants, p.Val37Ile and p.Val95Met, were more frequent in the patients’ group with statistical significance.Discussion: Our results allow for the p.Arg127His and p.Val153Ile variants to comply with polymorphism criteria and support the pathogenicity of p.Val37Ile and p.Val95Met variants. Moreover, two cases of moderate hearing loss were explained by the p.Val37Ile/p. Asn206Ser genotype, substantiating both the pathogenicity of such variants and the hypothesis that compound heterozygosity with p.Ans206Ser is associated with mild-moderate genotypes.Conclusion: Understanding the role of the variants is essential in order to provide genetic counselling to patients and their families. We explored a set of uncommon GJB2 variants that comprised 12% of the hearing-impaired patients in this study, supporting the relevance of their description.

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Genetic examination of children with hearing impairment in the astrakhan region

Russian otorhinolaryngology ◽

10.18692/1810-4800-2020-5-44-50 ◽

2020 ◽

Vol 19 (5) ◽

pp. 44-50

Author(s):

E. A. Grigor’eva ◽

◽

E. A. Ivanova ◽

T. G. Markova ◽

S. S. Chibisova ◽

...

Keyword(s):

Hearing Impairment ◽

Russian Federation ◽

Single Gene ◽

Gene Mutations ◽

Ethnic Composition ◽

Gjb2 Gene ◽

Compound Heterozygous ◽

Recessive Mutations ◽

Genetic Examination ◽

The Russian Federation

To study the prevalence of mutations in the GJB2 gene in deaf and deaf children in the Astrakhan region and compare them with the frequency of mutations in children with hearing impairment living in other regions of the Russian Federation taking into account regional characteristics. This work describes the results of epidemiological, audiological analysis, medical and genetic examination of children. We examined 6 frequent recessive mutations in the GJB2 gene in a group of 79 hearing impaired children registered with the Regional Center for Hearing Rehabilitation. Mutations were detected in 36 children (46%), with two mutations found only in 18 children (23%), and another 18 children were carriers of the same mutation. In 9 children (11.5%), the 35 delG mutation was detected in the homozygous state and in 9 children (11.5%) in the compound heterozygous state with a different mutation. We have shown that the results obtained do not correspond to the high prevalence of gene mutations (more than 50%) in groups of children with hearing impairment, established in most regions of the Russian Federation, as well as in several countries in Europe, China and Japan. The large number of carriers of a single gene mutation indicates the need to study the entire gene sequence and may be a consequence of the mixed ethnic composition of the subjects.

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Screening for Mitochondrial A1555G Mutation among Assortative Mating Hearing Impaired Families in South India: Some Vital Insights

New Frontiers in Medicine and Medical Research Vol. 1 ◽

10.9734/bpi/nfmmr/v1/3292f ◽

2021 ◽

pp. 17-27

Author(s):

Pavithra Amritkumar ◽

C. R. Srikumari Srisailapathy

Keyword(s):

Assortative Mating ◽

South India ◽

Hearing Impaired ◽

A1555g Mutation

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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)

Genes ◽

10.3390/genes10060429 ◽

2019 ◽

Vol 10 (6) ◽

pp. 429 ◽

Cited By ~ 5

Author(s):

Olga L. Posukh ◽

Marina V. Zytsar ◽

Marita S. Bady-Khoo ◽

Valeria Yu. Danilchenko ◽

Ekaterina A. Maslova ◽

...

Keyword(s):

Rare Variant ◽

Gjb2 Gene ◽

Exon 2 ◽

Southern Siberia ◽

Mutational Spectrum ◽

Recessive Mutations ◽

High Prevalence ◽

Sporadic Cases ◽

Different Populations ◽

Tyva Republic

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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