关键词: Waardenburg综合征, EDNRB基因, PAX3基因, 基因突变

Abstract:

Objective To report genetic and clinical features of two Waardenburg syndrome families. Design Retrospective case series. Participants Two Waardenburg syndrome families, four patients, were collected from Beijing Tongren Hospital in 2018. Methods The medical history, abnormalities of hair, and skin pigmentation of the probands and the affected members in the two families were recorded. The probands and affected members underwent a detailed ophthalmic evaluation and auditory examinations. Peripheral blood were collected from two probands and their family members and the relationships of the members and pedigree diagrams were recorded. The DNA of two probands were sequenced with six genes lead to Waardenburg syndrome with Sanger sequencing. The online bioinformatics analysis software were used to predict the pathogenicity of the detected mutations, and the pathogenic mutations were performed the co-segregated analysis. Finally, according to the American College of Medical Genetics and Genomics (ACMG) pathogenic grading guidelines, the detected mutations were classified into the five levels. Main Outcome Measures Pathogenic mutation, eye and systemic pigment abnormalities， fundus and audiometry. Results EDNRB and PAX gene mutations were detected in two Waardenburg syndrome families, caused Waardenburg syndrome type I and Waardenburg syndrome type IV, respectively. The probands of both families had abnormal iris pigmentation, poor hearing, whitening of the hair and wide roots of the nose, but the degree and location were different. All confirmed or suspected members of both families had white hair or prefrontal white hair without abnormal skin pigmentation. Conclusion The study identified the pathogenic genes of two Waardenburg syndrome families and expanded the mutation spectrum of PAX3 and EDRRB genes. Genetic testing is an important means for differential and subtypes diagnosis of the suspected Waardenburg syndrome.

Key words: Waardenburg syndrome, EDNRB gene, PAX3 gene, gene mutation