Abstract:

Objective To investigate the carrier status of hearing loss gene mutations beyond the 9 commonly screened variants (GJB2: 35delG,235delC, 176del16bp, 299-300delAT; SLC26A4: 919-2A>G,2168A>G;12S rRNA:1494C>T,1555A>G; GJB3: 538C>T) among pediatric hearing loss patients in Jiangxi, China. Methods A total of 118 pediatric patients diagnosed with hearing impairment at Jiangxi Provincial Children's Hospital between January 1, 2018 and September 30, 2021 were screened. Patients who tested negative for the 9 variants or carried a single heterozygous mutation in GJB2 and/or SLC26A4 were included. Multiplex polymerase chain reaction (PCR) amplification and capture techniques were employed to detect all known pathogenic variants in GJB2, SLC26A4 and 12S rRNA genes. Variant patterns were analyzed. Results Totally, 19 additional variants were detected among 118 patients, including 2 in the GJB2 gene, 16 in the SLC26A4 gene, and 1 in the 12S rRNA gene. Among these patients, 32 cases exhibited the GJB2 c.109G>A variant, with 20 in homozygous form. Additionally, one presented with the GJB2 c.139G>T heterozygous variant. Among the 16 other pathogenic variants detected in the SLC26A4 gene, the c.1229C>T variant appeared 3 times, while c.916dup, c.1226G>A and c.1905G>A were detected twice. The remaining variants (c.2T>G, c.84C>A, c.349del, c.757A>G, c.1079C>T, c.1174A>T, c.1286C>A, c.1692dup, c.1707+5G>A, c.1983C>A, c.2000T>C and c.2162C>T) were identified once. One case carried the m.1027A>G variant in the mitochondrial 12S rRNA gene. Conclusions In addition to the 9 commonly screened mutations, the GJB2 c.109G>A variant shows the highest detection rate in pediatric hearing impairment patients in Jiangxi. A diverse range of additional SLC26A4 gene variants is identified, with c.1229C>T, c.1226G>A, c.916dup and c.1905G>A occurring at relatively high frequencies and warranting further attention. The use of multiplex PCR amplification and capture techniques significantly improves the detection rate of gene variants in pediatric hearing impairment patients.

Key words: Hearing loss gene, GJB2, SLC26A4, 12S rRNA, Multiplex polymerase chain reaction amplification and capture technique