Clinical Characteristics and Identification of Pathogenic Variant in a Large Chinese Family With Waardenburg Syndrome.

Background: Waardenburg syndrome is a genetic disorder characterized by sensorineural hearing loss and abnormal pigmentation. This study aims to explore the pathogenic variant in a large Waardenburg syndrome family and provide a theoretical basis for prenatal diagnosis of related family members.

Methods: The clinical phenotype of the family members was analyzed. DNA was extracted from collected peripheral blood samples, and then exome sequencing and Sanger sequencing were performed. The pathogenicity of the genetic variant was evaluated by bioinformatics analysis. Amniocentesis was performed on the proband's mother (III13) to collect amniotic fluid samples for prenatal diagnosis.

Results: There were 13 patients in the family. Most of the patients presented with deafness and abnormal pigmentation of hair or eyes, which was consistent with the diagnosis of Waardenburg syndrome type 2. Exome sequencing revealed a heterozygous variant of the SOX10 gene (NM_006941.4: c.386T>C (p.Leu129Pro)) in the proband. Sanger sequencing showed that the variant co-segregated with the disorder in this family. This variant has not been previously reported in relevant databases. The site p.Leu129 was highly conserved among various species and was important for protein structure and function.

Conclusion: In this study, we reported a family with autosomal dominant Waardenburg syndrome type 2 and identified a heterozygous variant of the SOX10 gene by exome sequencing. In addition, prenatal diagnosis and genetic counseling were provided to the family related individual.