Connexin 26 gene mutations in congenitally deaf children - Pitfalls for genetic counseling

Objective: To evaluate difficulties encountered in genetic counseling in de af children carrying connexin 26 gene (CX26 or GJB2) mutations. Design: Prospective study. Setting: Outpatients, tertiary referral center Patients: Ninety-six unrelat ed deaf children in whom CX26 mutations had been detected consecutively. Ch ildren were recruited to a center for genetic counseling for deaf children, and all had congenital deafness, sporadic or familial. Results: In 63 children, deafness was clearly a DFNB1 form with autosomal r ecessive inheritance: 47 of the 63 were homozygous for the most frequent mu tation, the deletion of G at position 35 (35delG); 16 of 63 carried on both alleles of CX26 frameshift or stop mutations, or missense mutations affect ing a critical region of the gene. In 33 of 96 children, genetic counseling was difficult: 21 of 33 had a single mutation detected, 11 of 33 had new m issense mutations or mutations whose pathogenicity remains debated in the l iterature, and 1 of 33 had a genotype with both a recessive mutation (35del G) and a mutation acting as a dominant mutation. Conclusions: Interpretation of results for the molecular diagnosis of mutat ions in the connexin 26 gene is difficult in almost one third of cases. Clo se collaboration between geneticists familiar with deafness and otolaryngol ogists is essential to provide a high standard of genetic advice.