GJB2 AND GJB6 GENETIC VARIANT CURATION IN A NON-SYNDROMIC HEARING LOSS COHORT FROM ARGENTINA

BUONFIGLIO, PAULA I.; BRUQUE, CARLOS D.; MENAZZI, SEBASTIÁN; FRANCIPANE, LILIANA; LOTERSZTEIN, VANESA; ELGOYHEN, ANA BELÉN; DALAMÓN, VIVIANA KARINA

Virtual

Congreso; Reunión Conjunta SAIC. SAI. AAFE. NANOMED-AR; 2021

Hereditary hearing impairment affects 1-500 newborn children. It ischaracterized by the large number of genes involved (more than100) and its phenotype heterogeneity. Despite the wide genetic varietyof hearing impairment, the most commonly mutated genes in severeto profound autosomal recessive non-syndromic hearing lossare GJB2 and GJB6, accounting for nearly 50% of the cases in mostpopulations around the Mediterranean Sea. Molecular diagnosis enablesproper genetic counseling and medical prognosis to patients.Therefore, correct interpretation of the phenotypic consequences ofgenetic variants is crucial in genetic diagnosis, since discrepanciesin sequence variant interpretation and classification has been reportedto lead to serious impact in patient health maintenance.In thisstudy we aimed to identify the genetic causes of hearing loss andperformed a manual genetic variant curation following the AmericanCollege of Medical Genetics and Genomics/Association for MolecularPathology ACMG/AMP standards and hearing-loss-gene-specificcriteria of the ClinGen Hearing Loss Expert Panel.A total of 600patients were studied for genetic variants in GJB2 and GJB6 genesby Sanger Sequencing technique and Multiplex Gap-PCR, respectively.Overall, 48 different sequence variants were detected in ourcohort of patients, being the c.35delG the most common causativevariant identified. Besides, more than 50% of sequence variantswere reclassified from their previous categorization in ClinVar aftercareful manual analysis. These results provide an accurately analysedand interpreted set of variants to be taken into account byclinicians and the scientific community, and hence, aid the precisegenetic counseling to patients.