[Genetic and Phenotypic Analysis of Rare Variants Associated with Autosomal Recessive Hearing Loss]

To analyze the phenotype and genotype characteristics of autosomal recessive hearing loss caused by gene variants, and to provide genetic diagnosis and genetic counseling for patients and their families. Identification of gene variants by next generation sequencing in two sporadic cases of hearing loss at Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. The sequence variants were verified by Sanger sequencing.The pathogenicity of these variants was determined according to the American College of Medical Genetics and Genomics（ACMG） variant classification guidelines, in conjuction with clinical data. The probands of the two families have bilateral,severe or complete hearing loss.Four variants of were identified, including one pathogenic variant that has been reported, two likely pathogenic variants,and one splicing variant of uncertain significance. Patient I carries c. 3524dupA（p. Ser1176Valfs*14）, a reported pathogenic variant, and a splicing variant c. 10082+3G>A of uncertain significance according to the ACMG guidelines. Patient I was treated with bilateral hearing aids with satisfactory effect, demonstrated average hearing thresholds of 37.5 dB in the right ear and 33.75 dB in the left ear. Patient Ⅱ carries c. 7441_7442del（p. Leu2481Glufs*86） and c. 10250_10252del（p. Ser3417del）,a pair of as likely pathogenic variants according to the ACMG guidelines. Patient Ⅱ, who underwent right cochlear implantation eight years ago, achieved scores of 9 on the Categorical Auditory Performance-Ⅱ（CAP-Ⅱ） and 5 on the Speech Intelligibility Rating（SIR）. This study's discovery of the rare c. 7441_7442del variant and the splicing variant c. 10082+3G>A in the gene is closely associated with autosomal recessive hearing loss, expanding the variant spectrum. Additionally, the pathogenicity assessment of the splicing variant facilitates classification of splicing variations.