Characterisation of exon two of the GJB2 gene in Cubans with autosomal recessive prelingual isolated hearing loss
DOI:
https://doi.org/10.56294/saludcyt20251575Keywords:
connexin 26, non-syndromic, deafness, autosomal recessive, gab β 2 binding proteinAbstract
INTRODUCTION: Hearing loss is the most common neurological disorder in humans. In its prelingual form, it occurs in one in every 1,000 live births. The most common type is isolated autosomal recessive hearing loss, caused mainly by pathogenic variants of the GJB2 gene. The most common of these in all populations is c.35delG, located in exon two, which encodes this gene. This mutation has been identified in heterozygosity in Cubans with hearing loss. Given its high allelic heterogeneity, Sanger sequencing is recommended to confirm the molecular diagnosis. OBJECTIVE: To characterise exon 2 of the GJB2 gene in a series of Cuban patients with autosomal recessive prelingual isolated hearing loss. MATERIAL AND METHOD: A descriptive, cross-sectional study was conducted. From 379 cases in which molecular study was performed by allele-specific PCR of the pathogenic variant c.35delG, 13 heterozygotes were selected in which deletions D13S1830 and D13S1854 of the GJB6 gene had previously been ruled out. Sanger sequencing of exon 2 was performed, for which four specific oligonucleotides were designed to amplify two overlapping fragments to ensure complete analysis of the coding region of the GJB2 gene. Given the characteristics of the c.35delG mutation, two additional primers were included to analyse the start of exon 2. Information on the identified variants was sought on the ClinVar website. The audiometric characteristics of the patients were observed. Throughout the research, the principles of human research ethics were followed. RESULTS The c.427C>T variant was identified in three individuals, while the c.94C>T mutation was found in another, and c.139G>T in a fifth. The patients presented sensorineural hearing loss with severity levels exceeding 61 dB. CONCLUSION: Three pathogenic variants were identified in the coding region of the GJB2 gene, associated with severe to profound hearing loss.
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Copyright (c) 2025 Estela Morales Peralta , Mercedes Arceo Alvarez , Yuledmi Perdomo Chacón, Teresa Collazo Mesa, Katrin Beyer (Author)
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