Affiliation:
1. Department of Nephrology Children's Hospital of Nanjing Medical University Nanjing 210008 China
2. Nanjing Key Laboratory of Pediatrics Children's Hospital of Nanjing Medical University Nanjing 210008 China
Abstract
AbstractBiallelic Wnt ligand secretion mediator (WLS gene) variants are associated with Zaki syndrome (OMIM: #619648). Here, we report the first case with Zaki syndrome in the Chinese population. Whole‐exome gene sequencing (WES) identified compound heterozygous variants in the WLS gene (c.1427A > G; p.Tyr476Cys and c.415C > T, p.Arg139Cys; NM_001002292) in a 16‐year‐old boy presenting with facial dysmorphism, astigmatism, renal agenesis, and cryptorchidism. In vitro functional characterization showed that the two variants led to decreased WLS production and secretion of WNT3A, eventually affecting the WNT signal. We also found that the decreased mutant WLS expression can be rescued by 4‐Phenylbutyric acid (4‐PBA).
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Subject
Genetics (clinical),Genetics