Population-Specific Mutational Spectrum of Autosomal Recessive Nonsyndromic Hearing Loss in Croatian Roma: Implications for Clinical Genetics

Background/Objectives: Hearing impairment is a highly prevalent sensory disorder resulting from a variety of causes. A high proportion of autosomal recessive non-syndromic hearing impairment is linked to the GJB2 (OMIM 121011) gene which encodes for a gap junction protein, connexin-26. Alterations of genes that encode for connexins can lead to changes in cell ion content and cause hearing impairment. Methods: GJB2 gene polymorphisms (c.71G>A, p.Trp24*rs104894396; c.457G>A, p.Val153Ile, rs111033186; c.380G>A, p.Arg127His, rs111033196; c.109G>A, p.Val37Ile, rs72474224; and c.269T>C, p.Leu90Pro, rs80338945) were analyzed in the Roma population of Croatia. Loci were genotyped using the KASP method. Results: Altered alleles were detected on the loci c.71G>A, c.457G>A and c.380G>A and statistically significant differences in allele frequencies were noticed. Furthermore, in comparison to worldwide populations, the Roma population also shows statistically significant difference in allele frequency of these loci. Conclusions: This study reveals marked genetic differentiation among Croatian Roma particularly with respect to the c.71G>A variant. Characterizing such population-specific mutational heterogeneity is crucial for the accurate prevention, diagnosis, and clinical management of autosomal recessive nonsyndromic hearing loss.