A novel frameshift mutation of SOX10 identified in Waardenburg syndrome type 2

Abstract Waardenburg syndrome type 2 (WS2) is an autosomal dominant disorder characterized by congenital sensorineural hearing loss, blue iris, and abnormal pigmentation of the hair and skin. WS2 is genetically heterogeneous, often resulting from pathogenic mutations in SOX10 gene. We identified a novel heterozygous frameshift mutation in SOX10 (NM_006941.4: c.22delT, p.S8Rfs*5) in a two-generation Chinese family with WS2 through whole exome sequencing. This mutation was present in both the proband, who exhibited typical features of hearing loss and pigmentation abnormalities, and his father, who showed only mild facial features. Quantitative real-time PCR revealed that the frameshift mutation leads to a reduced expression levels of SOX10 in the peripheral blood of mutation carriers. Our findings expand the spectrum of pathogenic mutations in SOX10 associated with WS2, providing valuable information for prenatal diagnosis and preimplantation screening, and underscore the role of genetic diagnosis in identifying atypical patients.