https://scholars.lib.ntu.edu.tw/handle/123456789/637008
標題: | Genetic Factors Contribute to the Phenotypic Variability in GJB2-Related Hearing Impairment | 作者: | Chiang Yu-ting PEI-HSUAN LIN Lo, Ming-Yu HSIN-LIN CHEN Lee, Chen-Yu Tsai, Cheng-Yu Lin, Yin-Hung Tsai, Shih-Feng TIEN-CHEN LIU Hsu, Chuan-Jen PEI-LUNG CHEN Jacob Shujui Hsu CHEN-CHI WU |
公開日期: | 7-九月-2023 | 卷: | 25 | 期: | 11 | 來源出版物: | The Journal of molecular diagnostics : JMD | 摘要: | Recessive variants in GJB2 are the most important genetic cause of sensorineural hearing impairment (SNHI) worldwide. Phenotypes vary significantly in GJB2-related SNHI, even in patients with identical variants. For instance, patients homozygous for the GJB2 p.V37I variant, which is highly prevalent in the Asian populations, usually present with mild-to-moderate SNHI; yet severe-to-profound SNHI is occasionally observed in approximately 10% of p.V37I homozygotes. To investigate the genomic underpinnings of the phenotypic variability, we performed next-generation sequencing of GJB2 and other deafness genes in 63 p.V37I homozygotes with extreme phenotypic severities. We identified additional pathogenic variants of other deafness genes in 5 of the 35 patients with severe-to-profound SNHI. Furthermore, we conducted case-control association analyses for 30 unrelated p.V37I homozygotes with severe-to-profound SNHI against 28 p.V37I homozygotes with mild-to-moderate SNHI, and 120 population controls from the Taiwan Biobank. We found that the severe-to-profound group had a higher frequency of the crystallin lambda 1 (CRYL1) variant (rs14236), located upstream of GJB2, than the mild-to-moderate and Taiwan Biobank groups. Our results demonstrated that pathogenic variants in other deafness genes and a possible modifier, the CRYL1 rs14236 variant, may contribute to phenotypic variability in GJB2-realted SNHI, highlighting the importance of comprehensive genomic surveys to delineate the genotype-phenotype correlations. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/637008 | ISSN: | 15251578 | DOI: | 10.1016/j.jmoldx.2023.07.005 |
顯示於: | 醫學系 |
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