Genetic testing for hereditary hearing loss: Connexin 26 (GJB2) allele variants and two novel deafness-causing mutations (R32C and 645-648delTAGA)

Mutations in GJB2 are the most common cause of hereditary congenital hearin g loss in many countries and are found in about half of persons with severe -to-profound congenital autosomal recessive non-syndromic hearing loss (ARN SE). We report the results of GJB2 mutation screening in 209 consecutive pe rsons with congenital dearness of indeterminate etiology using an allele sp ecific polymerase chain reaction assay, single-strand conformational polymo rphism analysis, and direct sequencing. GJB2 allele variants were detected in 74 of 209 deaf individuals (35%). Over one-fourth of screened individual s were either homozygous (n=31) or heterozygous (n=24) for the 35delG mutat ion. Of those with the 35delG mutation, 51 (92.7%) were diagnosed with GJB2 -related deafness. Nineteen persons were identified with other GJB2 allele variants - two novel deafness-causing mutations (R32C, 645-648delTAGA), one mutation of unknown significance (E47K), and one benign polymorphism (I128 I), While these data enable health care professionals to provide parents an d patients with improved genetic counseling data, difficulty still exists i s determining whether some missense mutations compromise auditory function and are deafness-causing. Hum Mutat 16:502-508, 2000. (C) 2000 Wiley-Liss, Inc.