GJB2 Mutations in the Swiss Hearing Impaired

In Brief Objective Mutations in the GJB2 gene encoding connexin 26 (Cx26) protein are a major cause for nonsyndromic autosomal recessive and sporadic deafness. However, its contribution to hearing impairment in Switzerland remains undefined. To determine the frequency and type of GJB2 mutations in the Swiss hearing-impaired population diagnosed under the age of 2 yr and at 2 yr and older and to assess the effectiveness of denaturing high-performance liquid chromatography (DHPLC) in screening for mutation in GJB2. Methods Thirty-four patients with hearing impairment underwent mutation screening of the single coding exon of GJB2 with DHPLC followed by bidirectional sequencing to identify sequence alterations. Results GJB2 mutations were more common in children diagnosed with hearing impairment under the age of 2 yr compared to the group 2 yr and older. In patients under age 2 yr, 9 of 20 (45%) harbored 13 GJB2 mutations including a common 313del14nt mutation; four of these patients were homozygous or compound heterozygous for GJB2 mutations. In contrast, 2 of 14 patients in the 2 yr and older group (14%) had a single mutation in GJB2. The 35delG mutation was exclusively found in 5 patients under the age of 2 yr. DHPLC for mutation screening was 100% sensitive and 83% specific for detecting sequence alterations in GJB2. Conclusions In Switzerland, GJB2 mutations are a major cause of nonsyndromic hearing impairment in children under the age of 2. Similar to other populations, GJB2 mutations are uncommon in the affected Swiss patients identified after 2 yr. Although 35delG mutation is common in the hearing-impaired children under the age of 2, it was absent in patients diagnosed with hearing impairment after the age of 2. DHPLC is a highly sensitive tool for detection of GJB2 mutations. Mutations in GJB2 gene encoding connexin 26 (Cx26) protein are a major cause of nonsyndromic autosomal recessive and sporadic deafness. In this manuscript, the contribution of GJB2 mutations in the Swiss hearing impaired population diagnosed under the age of 2 years, and at 2 years and older, and the effectiveness of denaturing high-performance liquid chromatography (DHPLC) in screening for mutations in GJB2 is investigated. We determined that GJB2 mutations are a major cause of nonsyndromic hearing impairment in children diagnosed under the age of 2 while they are uncommon in children diagnosed at age older than 2 year. Further, we show that DHPLC is a highly sensitive tool for detection of GJB2 mutations.