The spectrum of GJB2 gene mutations in Algerian families with nonsyndromic hearing loss from Sahara and Kabylie regions.

Abstract Introduction DFNB1, caused by mutations of GJB2 or GJB6 , is the most prevalent genetic form of nonsyndromic (i.e., isolated) congenital deafness in countries located around the Mediterranean Sea. Because some mutations are restricted to specific ethnic-geographic groups, we studied the prevalence and spectrum of GJB2 / GJB6 mutations in deaf patients originating from two different Algerian regions, Kabylie and Sahara. Patients and methods Among 91 reportedly unrelated Algerian patients affected by prelingual deafness, 80 patients (41 from Kabylie and 39 from Sahara) were diagnosed with isolated deafness. All had profound deafness, except one patient with mild deafness. They were screened for the presence of GJB2 mutations by direct sequencing of the single coding exon of GJB2 . Patients without mutations were then screened for the presence of the most frequent two deletions of GJB6 : del( GJB6 -D13S1854) and del( GJB6 -D13S1830). Results Causative mutations were found in 13 and 8 patients from Kabylie and Sahara, respectively, accounting for more than a quarter of the cohort. The c.35delG, p.Gly12Valfs*2 mutation remains the most important mutation both in Kabylie (10 patients) and Sahara (7 patients). All detected patients were homozygous for this mutation. In addition, two other mutations (c.139G > T, p.Glu47* and c.167delT, p.Leu56Argfs*26) were found homozygous in one family each, and two patients were compound heterozygotes for (c.35delG p.Gly12Valfs*2/c.139G > T, p.Glu47*). No deletion of GJB6 was detected. Conclusion We confirm that mutations in GJB2 , mainly c.35delG, are one of the most prevalent causes of nonsyndromic congenital deafness in Algeria, whereas the del ( GJB6 -D13S1854) and del ( GJB6 -D13S1830) deletions of GJB6 contribute little, if any. Further investigation is needed to identify the cause of deafness in other patients without diagnostic.