关键词: Waardenburg综合征, DNA突变分析, 色素沉着异常, 听觉丧失, PAX3基因

Abstract: 【Abstract】 Objective To report a Chinese pedigree with autosomal dominant Waardenburg syndrome, and to identify causative gene mutations. Methods Clinical data and peripheral blood samples were collected from the proband and her parents. Genomic DNA was extracted, gene mutations were detected through a next?generation skin?targeted sequencing panel, and Sanger sequencing was performed to verify causative mutations. Results The proband clinically presented with irregular white patches on the abdomen and lower limbs, moderate to severe sensorineural deafness in the right ear, and iris heterochromia in both eyes. The proband′s mother presented with iris heterochromia in both eyes, epicanthus, early canities and thick eyebrows. In the family, both the proband and her mother were diagnosed with Waardenburg syndrome. A causative frameshift mutation c.976?977delinsT（p.Thr327Profs*54） was identified in both the proband and her mother, which caused the AG to TT base substitution at positions 976 - 977 in the coding region of exon 7 of the PAX3 gene, resulted in a frameshift from the amino acid position 327 to 54 in the PAX3 protein （threonine was substituted by proline at amino acid position 327）. The proband′s father showed a normal phenotype, and his genetic test results were negative. Conclusion The novel frameshift mutation c.976?977delinsT （p.Thr327Profs*54） in the PAX3 gene may contribute to the clinical phenotype of the patients with Waardenburg syndrome in the family.

Key words: Waardenburg sydrome, DNA mutational analysis, Pigmentation disorders, Hearing loss, PAX3 gene