In a study of 35 families with autosomal recessive bilateral sensorineural hearing loss (220290), Abe et al. (2000) found a deletion of a single C nucleotide at position 235 of the GJB2 gene in 8 of 11 Japanese families in which a mutation in the GJB2 gene was found. The 235delC mutation, which causes a frameshift at codon 79 resulting in a truncated polypeptide, was found in homozygosity in 2 families and in compound heterozygosity with other mutations in 5 families. One family was heterozygous for the 235delC mutation with no other mutation being detected. The deletion was also found in 2 of 192 control alleles.
Kudo et al. (2000) found that the most common GJB2 mutation among 39 Japanese patients with prelingual deafness was 235delC. The mutation was found in 7 of 10 mutant alleles and in 2 of 203 unrelated normal individuals in the Japanese population.
Liu et al. (2002) found that the 235delC mutation is the most prevalent one causing deafness in Chinese. It accounted for 81% of the pathologic alleles in multiplex cases and 67% in simplex cases. Analysis of the affected haplotypes in patients with a homozygous 235delC mutation yielded evidence for a single origin of the mutation. Carrier frequency in control subjects with normal hearing was 1.3%.
Yan et al. (2003) stated that the high frequency of the 235delC mutation in multiple East Asian populations suggested that it results from recurrent deletion at a mutation hotspot or is derived from a common ancestral founder. Among East Asians, they observed significant linkage disequilibrium between 235delC and 5 linked polymorphic markers, suggesting that 235delC was derived from a common founder. The detection of this mutation only in East Asians, but not in Caucasians, and the small chromosomal interval of the shared haplotype suggested that it is an ancient mutation that arose after the divergence of Mongoloids and Caucasians. The finding that this mutation appears on a single haplotype argues against the possibility of recurrent mutation as the explanation for the high frequency of the allele.
Dai et al. (2007) collected DNA specimens from 3,004 patients with nonsyndromic hearing impairment from 26 regions of China, 368 Han Chinese and 98 Uigur controls, and screened for the 235delC mutation. Overall, 488 patients (16.3%) carried at least 1 235delC mutant allele, with 233 (7.8%) homozygotes and 255 (8.5%) heterozygotes. Therefore, within the subpopulations examined, the frequency varies from 0 to 14.7% for 235delC homozygotes and from 1.7 to 16.1% for heterozygotes. Dai et al. (2007) found that Chinese patients with nonsyndromic hearing loss have a higher frequency of the 235delC mutation than that of other Asian populations.
In 2 unrelated Chinese patients with autosomal recessive profound hearing impairment, Liu et al. (2009) found compound heterozygosity for the 235delC mutation in the GJB2 gene and a mutation in the GJB3 gene (603324.0011 and 603324.0012, respectively). The findings were consistent with digenic inheritance (see 220290). The unaffected parents were heterozygous for 1 of the mutant alleles.
