摘要
Mutations in the GJB2 gene are the most frequently found mutations in patients with nonsyndromic hearing impairment. However, the mutation spectrum and prevalence of mutations vary among different ethnic groups. Every year, 30, 000 babies are born with congenital hearing impairment in China. In order to provide appropriate genetic testing and counseling to the family, we investigated the molecular etiology of nonsyndromic deafness in 135 unrelated school children attending Chifeng Municipal Special Education School in Inner Mongolia, China. The coding exon of the GJB2 gene was PCR amplified and sequenced. In addition, the 12S rRNA gene and tRNAser(UCN) of mitochondrial genome were screened for mutations responsible for hearing impairment. Sixty four GJB2 mutant alleles, including 60 confirmed pathogenic alleles and 4 unclassified variants, were identified in 31.1% (42/135) of the subjects. Twenty two subjects carried two pathogenic mutations and 20 subjects carried one mutant allele, including one subject with one autosomal dominant mutation. The 235delC was the most common mutation accounting for 65.6%(42/64) GJB2 mutant alleles. When compared to other Asian populations, our subject cohort had higher frequency of 235delC mutation than the Japanese population. The GJB2 mutant alleles account for 23.7% (64/270) of all chromosomes responsible for nonsyndromic hearing impairment. Testing of the 4 most prevalent deleterious frame shift mutations(235delC, 29900delAT, 17691del16, and 56005ins46) in this cohort detected 90% of all GJB2 mutant alleles. These results demonstrate that effective genetic testing of the GJB2 gene for patients and families with nonsyndromic hearing impairment is possible in the Chinese population. Since the most common 309kb GJB6 deletion is not detected and only one 1555 A>G mutation in mitochondrial DNA is detected in our patients, investigation of mutations in other nuclear genes and/or environmental factors responsible for nonsyndromic hearing impairment in the Chinese population is necess
Mutations in the GJB2 gene are the most frequently found mutations in patients with nonsyndromic hearing impairment. However, the mutation spectrum and prevalence of mutations vary among different ethnic groups. Every year, 30, 000 babies are born with congenital hearing impairment in China. In order to provide appropriate genetic testing and counseling to the family, we investigated the molecular etiology of nonsyndromic deafness in 135 unrelated school children attending Chifeng Municipal Special Education School in Inner Mongolia, China. The coding exon of the GJB2 gene was PCR amplified and sequenced. In addition, the 12S rRNA gene and tRNAser(UCN) of mitochondrial genome were screened for mutations responsible for hearing impairment. Sixty four GJB2 mutant alleles, including 60 confirmed pathogenic alleles and 4 unclassified variants, were identified in 31.1% (42/135) of the subjects. Twenty two subjects carried two pathogenic mutations and 20 subjects carried one mutant allele, including one subject with one autosomal dominant mutation. The 235delC was the most common mutation accounting for 65.6%(42/64) GJB2 mutant alleles. When compared to other Asian populations, our subject cohort had higher frequency of 235delC mutation than the Japanese population. The GJB2 mutant alleles account for 23.7% (64/270) of all chromosomes responsible for nonsyndromic hearing impairment. Testing of the 4 most prevalent deleterious frame shift mutations(235delC, 299_300delAT, 176_191del16, and 560_605ins46) in this cohort detected 90% of all GJB2 mutant alleles. These results demonstrate that effective genetic testing of the GJB2 gene for patients and families with nonsyndromic hearing impairment is possible in the Chinese population. Since the most common 309kb GJB6 deletion is not detected and only one 1555 A>G mutation in mitochondrial DNA is detected in our patients, investigation of mutations in other nuclear genes and/or environmental factors responsible for nonsyndromic hearing impairment in the Chinese population is
