A novel mutation in PAX3 associated with Waardenburg syndrome type I in a Chinese family

Abstract

Conclusion The novel compound heterozygous mutation in PAX3 was the key genetic reason for WS1 in this family, which was useful to the molecular diagnosis of WS1. Purpose Screening the pathogenic mutations in a four generation Chinese family with Waardenburg syndrome type I (WS1). Methods WS1 was diagnosed in a 4-year-old boy according to the Waardenburg syndrome Consortium criteria. The detailed family history revealed four affected members in the family. Routine clinical, audiological examination, and ophthalmologic evaluation were performed on four affected and 10 healthy members in this family. The genetic analysis was conducted, including the targeted next-generation sequencing of 127 known deafness genes combined with Sanger sequencing, TA clone and bioinformatic analysis. Results A novel compound heterozygous mutation c.[169_170insC;172_174delAAG] (p.His57ProfsX55) was identified in PAX3, which was co-segregated with WS1 in the Chinese family. This mutation was absent in the unaffected family members and 200 ethnicity-matched controls. The phylogenetic analysis and three-dimensional (3D) modeling of Pax3 protein further confirmed that the novel compound heterozygous mutation was pathogenic.

Keywords:

• Novel mutation
• PAX3
• targeted next-generation sequencing
• WS1

Acknowledgements

We sincerely thank all the family members for their participation and co-operation in this study.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Funding information

This work was supported by grants from the National 973 Basic Research Program of China (No. 2014CB541703 to Haibo Wang), the research special fund for public welfare industry of health (201202001), grants from the National Natural Science Foundation of China (81470693 to Haibo Wang, 81470704 to Xiaohui Bai, 81200744 to Daogong Zhang), grants from the Natural Science Foundation of Shandong Province (ZR2014HM022 to Xiaohui Bai, ZR2014HP064 to Fengguo Zhang), a grant from the Science and Technology Development Program of Shandong Province (2012G0021838 to Yuechen Han, 2013GGB14087 to Jianfen Luo).