MITF Is Mutated in Type 1 Waardenburg Syndrome With Unusual Phenotype.

Background: Waardenburg syndrome (WS) is a rare disorder characterized by varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair and skin. WS is classified into four subtypes (WS1-WS4) based on additional symptoms. Dystopia canthorum is a hallmark of WS type 1. There are two genes linked to WS type 1, including PAX3 and EDNRB.

Objective: This study aimed to investigate the genetic etiology of WS type 1 in a pair of twins from China with profound hearing loss, blond hair and eyebrows, dystopia canthorum, and brown irides.

Methods: The target capture sequencing and Whole-exome sequencing were performed to detect mutations in WS-related genes.

Results: A novel de novo frameshift mutation, p.L341Rfs*18 in MITF was identified in the twins. Hearing thresholds showed substantial improvements following cochlear implantation with a pure-tone average of 30 dB in free-field conditions.

Conclusions: The study showed the new genotype-phenotype correlations of MITF to WS type 1. Further molecular analysis is necessary to reappraise the current classification on WS.