Identification and functional analysis of a novel mutation in the PAX3 gene associated with Waardenburg syndrome type I

Publication date: 5 February 2018
Source:Gene, Volume 642
Author(s): Zhijie Niu, Jiada Li, Fen Tang, Jie Sun, Xueping Wang, Lu Jiang, Lingyun Mei, Hongsheng Chen, Yalan Liu, Xinzhang Cai, Yong Feng, Chufeng He
Waardenburg syndrome type 1 (WS1) is a rare autosomal dominant genetic disorder of neural crest cells (NCC) characterized by congenital sensorineural hearing loss, dystopia canthorum, and abnormal iris pigmentation. WS1 is due to loss-of-function mutations in paired box gene 3 (PAX3). Here, we identified a novel PAX3 mutation (c.808C>G, p.R270G) in a three-generation Chinese family with WS1, and then analyzed its in vitro activities. The R270G PAX3 retained nuclear distribution and normal DNA-binding ability; however, it failed to activate MITF promoter, suggesting that haploinsufficiency may be the underlying mechanism for the mild WS1 phenotype of the study family.

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