Case Report: Identification of a novel truncation mutation in PAX3 associated with Waardenburg syndrome type 1 in a Chinese family

Background Waardenburg syndrome (WS) is a rare autosomal dominant disorder clinically classified into four subtypes. These subtypes exhibit clear genotype–phenotype correlations involving pathogenic variants in genes such as PAX3, MITF, EDNRB/EDN3 , and SOX10 . PAX3 variants are primarily linked to Type 1 (WS1), making molecular testing essential for diagnosis. Methods Whole-exome sequencing (WES) was employed to identify disease-causing variants, followed by Sanger sequencing for validation in a Han Chinese family with a clinical diagnosis of WS1. Results WES of affected family members identified a novel heterozygous frameshift variant, PAX3 :c.57delC (p.Tyr20Thrfs * 90). Sanger sequencing validated this variant, confirming its presence in all affected individuals (I-2, II-3, and III-1) and absence in unaffected relatives. This segregation pattern is consistent with autosomal dominant inheritance. Conclusion This novel PAX3 truncating variant expands the known variantal spectrum associated with WS1 and provides new molecular insights that could enhance the diagnostic precision for patients with this disorder.