A novel noncanonical splicing pathogenic variant in PAX3 associated with Waardenburg Syndrome type 1 in an Iranian family

Abstract Background Waardenburg syndrome type 1 (WS1) is an uncommon autosomal dominant (AD) genetic disorder. The primary cause of WS1 has been shown to be the pathogenic variants of PAX3 , which encodes a protein that belongs to the paired box family (Paired Box 3). Variable manifestations of sensorineural hearing impairment, pigmentation abnormalities, and other clinical signs have been observed in individuals with WS1. Here, we report an Iranian pedigree affected by WS1, which was caused by a novel pathogenic splicing variant in PAX3 . Materials and methods WS1 was diagnosed in a 5-year-old girl according to the Waardenburg Syndrome Consortium criteria. According to a thorough family history, four relatives were affected. Exome sequencing (ES), combined with Sanger sequencing, was used in genetic studies. Results We identified a novel noncanonical splicing variant, NM_181458.4: c.86-3C > G, in PAX3 . In addition, the patient’s father was heterozygous for this variant. Conclusions This study highlights phenotypic variability in Iranian WS1 patients and demonstrates that ES has enabled us to better understand genetic diagnosis and expand the range of WS1 genetic variants.