Targeted exome sequencing for molecular diagnosis of pediatric Alport syndrome in southwest China

Cong ZhouYuanyuan XiaoXing WeiJing Wang^*Shanling Liu^*

• West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, China

Background: Alport syndrome (AS) is an inherited disorder affecting basement membrane collagen IV. AS is characterized by hematuria and progressive renal failure, which are accompanied by high-frequency sensorineural deafness and ocular changes. AS is caused by collagen type IV α3 chain (COL4A3), α4 chain (COL4A4), and α5 chain (COL4A5) variants. We aimed to identify the genetic variants in a cohort of 20 children with clinically suspected AS in southwest China. Results: Twenty-one COL4A3, COL4A4, and COL4A5 variants were detected in twenty probands. Sixteen (16/21, 76.2%) and five (5/21, 23.8%) of these variants were classified as pathogenic/likely pathogenic and uncertain significance, respectively, according to the criteria of the American College of Medical Genetics and Genomics. A total of 11 (11/21, 52.4%) and 10 (10/21, 47.6%) variants were known and novel, respectively. Conclusions: We performed molecular diagnosis on 15 patients using targeted exome sequencing. Our findings indicate additional COL4A3, COL4A4, and COL4A5 variants involved in AS, having implications for genetic diagnosis, therapy, and counseling of affected families.