Molecular Genetic Analyses Of Two Chinese Families With Nonsyndromic Hearing Impairment

Hearing impairment is a partial decrease or complete loss of one's ability to detect sounds and occurs with structural or functional impairment and/or damage of the hearing system. Hearing impairment is the most common human disorder of the auditory system and approximately 1/1000 children are born with congenital hearing loss. Damages in any part of the auditory system can cause hearing impairment. Genetic factors are the most important factor that causes hearing impairment. More than 50% of the congenital hearing impairment cases are caused by genetic factors. With the rapid advances in molecular genetic technologies, many genes for hearing impairment have been cloned or identified including 23 genes for autosomal recessive hearing impairment 21 genes for the autosomal dominant form of the disease. These genetic studies have provided significant insights into the physiological and pathological mechanisms of hearing impairment. The present study employed the human molecular genetic approach to characterize two Chinese families with nonsyndromic hearing impairment (NSHI).We recruited the two NSHI families from Jiangsu Province of China: one family was from the city of Yancheng (referred to as family 1) and the other was from the city of Sheyang (family 2). Family 1 exhibits an autosomal recessive mode of inheritance and family 2's inheritance is autosomal dominant. For family 1, we carried out linkage analysis with microsatellite markers flanking all known autosomal recessive NSHI genes and linked the causative gene in the family to polymorphic microsatellite marker D13S175. Direct DNA sequence analysis of the entire coding region of the GJB2 gene encoding connexin 26 (orβ-2 gap junction protein) revealed that a 1-bp homozygous deletion, 235delC, was responsible for the disease in the family. The deletion causes a frameshift and premature termination of translation. For family 2, we performed linkage analysis with the markers spanning all autosomal dominant NSHI genes. Our results excluded all the known autosomal dominant NSHI genes as the cause of the disease in the family, indicating that family 2 may harbor a new causative gene for NSHI. Future studies on family 2 may identify a new NSHI gene and provide significant insights into the physiological and pathological mechanisms of hearing impairment.