Case Report: A Novel PAX3 Mutation Associated With Waardenburg Syndrome Type 1

Abstract

Background: Waardenburg Syndrome Type 1 (WS1) is a rare hereditary disease, which is usually caused by the mutations of PAX3 (paired box 3). Here, we reported a pedigree with WS1, which was caused by a novel mutation in PAX3.Case Report: In this present report, a 10-year-old boy and his twin sister from a Han Chinese family presented with iris pigmentary abnormality, synophrys, and broad and high nasal root. Their father presented premature whitening of the hair, but no iris pigmentary abnormality. Their aunts presented the same clinical characteristics with the twins and premature graying of hair. However, none of the patients reported hearing loss. The clinical diagnosis of the four patients from this pedigree was WS1. The whole exome sequencing (WES) revealed a novel mutation (c.959-5T>G) in the PAX3 gene, which could be responsible for the observed pathogenic of WS1 in this pedigree. The genetic test confirmed the diagnosis of WS1 in the four patients from the studied pedigree.Conclusion: This present study demonstrated that genetic test based on WES, an effective alternative to regular clinical examinations, helps diagnose WS1. The newly identified PAX3 gene mutation can expand the understanding of WS1.

Waardenburg syndrome type 1: a case report of a family with a intragenic PAX3 deletion with no hearing loss or heterochromia of iris

“…This report provides further evidence that intragenic deletions in PAX 3 gene may cause a milder phenotype than PAX3 mutations. Many other reported cases of WS1 caused by deletions have been identified later in life because of the similar minimal presence of hallmark diagnostic features (Drozniewska and Haus, 2014; Choi et al ., 2018; Hu Q et al , 2021). This may need to be further studied for clarity, as more cases are reported.…”

“…Reports have shown a variety of presentations of WS1 caused by variants of PAX3 including other cases resulting from both partial and full deletions. For example, cases presenting with hearing loss and dystopia canthorum (Drozniewska and Haus, 2014; Choi et al ., 2018) and another with no hearing loss but heterochromia (Hu et al , 2021).…”