Prevalence of the c.35delG and p.W24X mutations in the GJB2 gene in patients with nonsyndromic hearing loss from North-West Romania

Spectrum and Frequency of the GJB2 Gene Mutations Among Latvian Patients with Prelingual Nonsyndromic Hearing Loss Mutations in the GJB2 gene (connexin 26) are the most common cause of congenital nonsyndromic severe-to-profound hearing loss. Sixty-five hearing impaired probands from Latvia were tested for mutations in the GJB2 gene to determine the percentage of hearing loss attributed to connexin 26 and the types of mutations in this population. A total of 62% of patients tested had GJB2 mutations. Four different mutations in the GJB2 gene were identified in Latvian patients with nonsyndromic sensorineural hearing loss: 35delG, 311-324del14, 235delC and M34T. The most prevalent mutation is 35delG (47% of all probands were homozygous and 8% compound heterozygous). Our findings support the conclusion that the 35delG mutation is the most prevalent GJB2 mutation and that it is the common cause of hereditary nonsyndromic hearing loss in populations of European descent.

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The spectrum of GJB2 gene mutations in Algerian families with nonsyndromic hearing loss from Sahara and Kabylie regions

International Journal of Pediatric Otorhinolaryngology ◽

10.1016/j.ijporl.2019.05.036 ◽

2019 ◽

Vol 124 ◽

pp. 157-160 ◽

Cited By ~ 3

Author(s):

Sonia Talbi ◽

Crystel Bonnet ◽

Farid Boudjenah ◽

Mohammed Tahar Mansouri ◽

Christine Petit ◽

...

Keyword(s):

Hearing Loss ◽

Gene Mutations ◽

Gjb2 Gene ◽

Nonsyndromic Hearing Loss

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The Functional Role of CONNEXIN 26 Mutation in Nonsyndromic Hearing Loss, Demonstrated by Zebrafish Connexin 30.3 Homologue Model

Cells ◽

10.3390/cells9051291 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1291

Author(s):

Hsuan-An Su ◽

Ting-Wei Lai ◽

Shuan-Yow Li ◽

Tzu-Rong Su ◽

Jiann-Jou Yang ◽

...

Keyword(s):

Hearing Loss ◽

Structural Changes ◽

Dominant Negative ◽

Gjb2 Gene ◽

Dominant Negative Effect ◽

Connexin 26 ◽

Transgenic Zebrafish ◽

Nonsyndromic Hearing Loss ◽

Transgenic Lines

Nonsyndromic hearing loss (NSHL) is of great clinical importance, and mutations in the GJB2 gene and the encoded human CONNEXIN 26 (CX26) protein play important roles in the genetic pathogenesis. The CX26 p.R184Q mutation was shown to be a dominant-negative effect in our previous study. Previously, we also demonstrated that zebrafish Cx30.3 is orthologous to human CX26. In the present study, we established transgenic zebrafish models with mutated Cx30.3 specifically expressed in the supporting cells of zebrafish inner ears driven by the agr2 promoter, to demonstrate and understand the mechanism by which the human CX26 R.184 mutation causes NSHL. Our results indicated that significant structural changes in the inner ears of transgenic lines with mutations were measured and compared to wild-type zebrafish. Simultaneously, significant alterations of transgenic lines with mutations in swimming behavior were analyzed with the zebrafish behavioral assay. This is the first study to investigate the functional results of the CX26 p.R184Q mutation with in vivo disease models. Our work supports and confirms the pathogenic role of the CX26 p.R184Q mutation in NSHL, with a hypothesized mechanism of altered interaction among amino acids in the connexins.

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Update of the spectrum of GJB2 gene mutations in 152 Moroccan families with autosomal recessive nonsyndromic hearing loss

European Journal of Medical Genetics ◽

10.1016/j.ejmg.2016.05.002 ◽

2016 ◽

Vol 59 (6-7) ◽

pp. 325-329 ◽

Cited By ~ 12

Author(s):

Amina Bakhchane ◽

Amale Bousfiha ◽

Hicham Charoute ◽

Sara Salime ◽

Mustapha Detsouli ◽

...

Keyword(s):

Hearing Loss ◽

Autosomal Recessive ◽

Gene Mutations ◽

Gjb2 Gene ◽

Nonsyndromic Hearing Loss

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Functional Evaluation of a Rare Variant c.516G>C (p.Trp172Cys) in the GJB2 (Connexin 26) Gene Associated with Nonsyndromic Hearing Loss

Biomolecules ◽

10.3390/biom11010061 ◽

2021 ◽

Vol 11 (1) ◽

pp. 61

Author(s):

Ekaterina A. Maslova ◽

Konstantin E. Orishchenko ◽

Olga L. Posukh

Keyword(s):

Hearing Loss ◽

Transmembrane Protein ◽

Amino Acid Position ◽

Indigenous Populations ◽

Gjb2 Gene ◽

Connexin 26 ◽

Functional Evaluation ◽

Nonsyndromic Hearing Loss ◽

Extracellular Loop ◽

Gene Encoding

Mutations in the GJB2 gene encoding transmembrane protein connexin 26 (Cx26) are the most common cause for hearing loss worldwide. Cx26 plays a crucial role in the ionic and metabolic homeostasis in the inner ear, indispensable for normal hearing process. Different pathogenic mutations in the GJB2 gene can affect all stages of the Cx26 life cycle and result in nonsyndromic autosomal recessive (DFNB1) or dominant (DFNA3) deafness and syndromes associating hearing loss with skin disorders. This study aims to elucidate the functional consequences of a rare GJB2 variant c.516G>C (p.Trp172Cys) found with high frequency in deaf patients from indigenous populations of Southern Siberia (Russia). The substitution c.516G>C leads to the replacement of tryptophan at a conserved amino acid position 172 with cysteine (p.Trp172Cys) in the second extracellular loop of Cx26 protein. We analyzed the subcellular localization of mutant Cx26-p.Trp172Cys protein by immunocytochemistry and the hemichannels permeability by dye loading assay. The GJB2 knockout HeLa cell line has been generated using CRISPR/Cas9 genome editing tool. Subsequently, the HeLa transgenic cell lines stably expressing different GJB2 variants (wild type and mutations associated with hearing loss) were established based on knockout cells and used for comparative functional analysis. The impaired trafficking of mutant Cx26-p.Trp172Cys protein to the plasma membrane and reduced hemichannels permeability support the pathogenic effect of the c.516G>C (p.Trp172Cys) variant and its association with nonsyndromic hearing loss. Our data contribute to a better understanding of the role of mutations in the second extracellular loop of Cx26 protein in pathogenesis of deafness.

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