Abstract:Objective To explore the pathogenic genes by analyzing the audiological and genetic characteristics of a family of Waardenburg syndrome(WS). Methods Questionnaire survey, audiological tests and whole body examinations were conducted for this family with WS, and the genetic map of this family was drawn to analyze its audiological and genetic characteristics. The candidate genes were identified using the EVA and Waardenburg gene diagnostic kits developed by Sanger sequencing technology and exon capture combined with next-generation sequencing technology. Results There were 3 generations in this family, and audiological tests were performed on 5 persons. Three patients had hair depigmentation, blue iris staining, widening inner canthus, and flat nose bridge, including 1 case of hearing loss and 1 case of congenital deafness. Common candidate gene identification by Sanger sequencing technology and screening by EVA, Waardenburg gene diagnostic kit (developed by Xiangya Hospital of Central South University using exon capture combined with next-generation sequencing technology) revealed mutations at two sites of the pathogenic gene PAX3, PAX3 NM_181457: exon6:c.803G>T and exon6:c.801delT. Of the two mutations on exon 6 of the PAX3 gene, c.803G>T mutation could cause the 268th codon encoded by the PAX3 gene to change from serine to isoleucine, and c.801delT mutation could cause the 267th codon to change from phenylalanine to leucine. They might cause subsequent base sequences to be disordered, leading to early termination of the protein at the 283rd codon, which may seriously affect the structure and function of the gene encoded protein, leading to disease. Conclusion Since mutations in the PAX3 gene were detected in both the mother and the child, the family is an autosomal dominant WS family due to PAX3 NM_181457: exon6:c.803G>T and exon6:c.801delT mutations. This study enriches the mutation profile of PAX3 gene and provided a reference for clinical molecular diagnosis and genetic counseling.
