Neurosensorial hearing loss. Diagnostic yield with NGS clinical exome.

Abstract

Background: Hearing loss is defined as total or partial loss of that function. Sensorineural hearing loss (SNHL) is the most common sensory impairment in humans (1:3000 newborns). Current studies report a diagnosis rate of around 50%.

Material and methods: Eleven patients with hearing loss were studied using a panel of 224 related genes. Sequencing (≥50x) was performed using Illumina technology, aligning to GRCh37. Variants were reported according to HGVS and confirmed with validated methods (invitae). Results were correlated with patients' phenotype and family history.

Results: Of the 11 cases (3 men/8 women), 1 was familial, seven (63.6%) showed a positive result, three cases (27.3%) had variants of uncertain significance (VUS), and one case had a negative result. Pathogenic variants (PV) were identified in the GJB2 gene (3 heterozygotes and one compound heterozygous). Compound heterozygotes were found in USH2A and ADGRV1. Two patients presented inner ear malformation.

Conclusion: The panel of genes related to hearing loss (226 genes) showed acceptable performance, detecting 63.6% of PV. The main gene found was GJB2, however, not in the same proportion as in other populations, and many in heterozygosis. Although some VP have been linked to both types of autosomal dominant (heterozygosity) and recessive (homozygosity) inheritance. There is no correlation with the degree of hearing loss and PV and its state in heterozygosis or homozygosis, VUS could very likely contribute to SNHL, modifying the phenotype. Segregation studies are necessary to be more precise in the diagnosis and in genetic counseling.