Molecular Diagnosis of Hearing Loss

Abstract

This unit discusses an approach to identifying a genetic etiology in an individual with nonsyndromic hearing loss. The unit begins with a discussion of the decision-making process that can be used to determine whether specific genes and/or a large gene panel should be used for molecular diagnosis of a patient presenting with nonsyndromic hearing loss. Next, two protocols are presented: (1) a full gene-sequencing assay to identify mutations in the GJB2 gene (encoding connexin 26), the most common cause of congenital hearing loss, and (2) an assay to detect the presence of the GJB6-D13S1830 deletion, a 342-kb deletion that causes hearing loss in homozygosity or in combination with a single GJB2 mutation. Finally, the unit ends with a strategy for determining the clinical significance of the test results, which can be challenging given the extensive genetic heterogeneity associated with hearing loss.