NGS Panel for Non-Syndromic Hearing Loss: Diagnostic Yield and Genotype-Phenotype Correlation in a Mexican Population
Hearing loss and NGS panel
Keywords:
hearing loss, NGS, Exome, GENETICSAbstract
Background: Hearing loss is defined as the total or partial loss of auditory function. Sensorineural hearing loss (SNHL) is the most common sensory disorder in humans, affecting approximately 1 in 3,000 newborns. Current molecular genetic studies report a diagnostic rate of around 50%.
Materials and Methods: Eleven patients with hearing loss were studied using a panel of 224 related genes. Sequencing (≥50x) was performed with Illumina technology, aligned to the GRCh37 human reference genome. Variants were reported according to HGVS (Human Genome Variation Society) guidelines and confirmed through validated methods (Invitae). Results were correlated with patient phenotype and family history.
Results: Of the 11 cases (3 males / 8 females), one had a positive family history. Seven patients (63.6%) had a positive genetic result, three (27.3%) presented variants of uncertain significance (VUS), and one had a negative result. Pathogenic variants (PVs) were identified in the GJB2 gene (three heterozygous and one compound heterozygous case). Compound heterozygous variants were found in USH2A and ADGRV1. Two patients showed inner ear malformations.
Conclusions: The hearing loss gene panel (224 genes) demonstrated acceptable diagnostic yield, identifying PVs in 63.6% of cases. GJB2 was the most frequently involved gene. No direct correlation was found between the degree of hearing loss and the presence of PVs; however, in some cases, there was an association with heterozygous or homozygous status. VUS may potentially contribute to non-syndromic sensorineural hearing loss (NSHL), possibly modifying the phenotype. Segregation studies are necessary to improve diagnostic precision and support genetic counseling.
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