Next-generation sequencing improves precision medicine in hearing loss.

Area of Science:

• Genetics
• Genomics
• Audiology

Background:

• Early etiological diagnosis of hearing loss is crucial for children's language and cognitive development.
• Hearing loss exhibits high genetic and allelic heterogeneity.
• Next-Generation Sequencing (NGS) gene panel testing accelerates diagnosis.

Purpose of the Study:

• To assess the clinical utility of a custom NGS GHELP panel for diagnosing hearing loss in Spanish individuals.
• To determine the prevalence of pathogenic variants (SNVs, indels, CNVs) in nuclear and mitochondrial genes associated with hearing loss.

Main Methods:

• Sequencing of 171 nuclear and 8 mitochondrial genes using a custom NGS GHELP panel.
• Analysis of 155 Spanish individuals with hearing loss.
• Identification of single nucleotide variants, indels, and copy number variants.

Main Results:

• A genetic diagnosis was achieved in 34% (52/155) of individuals, with 5% being syndromic.
• Autosomal recessive (87%) and dominant (12%) inheritance patterns were most common; mitochondrial (2%) was also identified.
• Common genes (GJB2, OTOF, MYO7A) and less frequent genes (TMC1, FGF3, mitCOX1) were implicated. Pathogenic copy number variants were found in 5% of diagnosed cases.

Conclusions:

• NGS panels effectively identify diverse pathogenic variants (SNVs, indels, CNVs) in nuclear and mitochondrial genes.
• This approach significantly reduces the diagnostic odyssey for hearing loss.
• Clinical implementation of genomic strategies, including newborn screening, is recommended.