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2025, Number 3

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Investigación en Discapacidad 2025; 11 (3)

NGS panel for non-syndromic hearing loss: diagnostic yield and genotype-phenotype correlation in a Mexican population

Marín-Ríos ND, Jiménez-Romo AE, Arenas-Sordo ML

Language: English
References: 25
Page: 101-108
PDF size: 829.85 Kb.


ABSTRACT

Introduction: hearing loss is defined as the total or partial loss of auditory function, constituting a major cause of disability worldwide. It 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%. Material and methods: eleven patients with hearing loss were studied using a panel of 224 related genes. Sequencing (≥ 50 ×) was performed with Illumina technology, aligned to the GRCh37 human reference genome. Variants were reported according to the Human Genome Variation Society (HGVS) guidelines and confirmed through validated methods (Invitae). Results were correlated with patient phenotype and family history. Results: of the 11 cases (three males and eight 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 (PV) 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 PV in 63.6% of cases. GJB2 was the most frequently involved gene, although not in the same proportion as observed in other populations, and often in heterozygous form. No direct correlation was found between the degree of hearing loss and the presence of PV; 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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