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Genetic testing for hereditary hearing loss: Connexin 26 (GJB2) allele variants and two novel deafness‐causing mutations (R32C and 645‐648delTAGA)
Author(s) -
Prasad S.,
Cucci R.A.,
Green G.E.,
Smith R.J.H.
Publication year - 2000
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/1098-1004(200012)16:6<502::aid-humu7>3.0.co;2-4
Subject(s) - missense mutation , genetics , hearing loss , allele , compound heterozygosity , biology , genetic counseling , mutation , genetic testing , gene , audiology , medicine
Mutations in GJB2 are the most common cause of hereditary congenital hearing loss in many countries and are found in about half of persons with severe‐to‐profound congenital autosomal recessive non‐syndromic hearing loss (ARNSHL). We report the results of GJB2 mutation screening in 209 consecutive persons with congenital deafness of indeterminate etiology using an allele‐specific polymerase chain reaction assay, single‐strand conformational polymorphism analysis, and direct sequencing. GJB2 allele variants were detected in 74 of 209 deaf individuals (35%). Over one‐fourth of screened individuals were either homozygous (n=31) or heterozygous (n=24) for the 35delG mutation. 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 (I128I). While these data enable health care professionals to provide parents and patients with improved genetic counseling data, difficulty still exists is determining whether some missense mutations compromise auditory function and are deafness‐causing. Hum Mutat 16:502–508, 2000. © 2000 Wiley‐Liss, Inc.