Abstract
Waardenburg syndrome (WS) is a group of autosomal-dominant hereditary conditions with a global incidence of 1/42,000. WS can be categorized into at least four types: WS1-4, and these are characterized by heterochromia iridis, white forelock, prominent nasal root, dystopia canthorum, hypertrichosis of the medial part of the eyebrows, and deaf-mutism. WS3 is extremely rare, with a unique phenotype (upper limb abnormality). Heterozygous mutations of PAX3 are commonly associated with WS1, whereas partial or total deletions of PAX3 are often observed in WS3 cases. Deletions, together with insertions, translocations, inversions, mobile elements, tandem duplications, and complexes, constitute structural variants (SVs), which can be fully and accurately detected by third-generation sequencing (TGS), a new generation of high-throughput DNA sequencing technology. In this study, after failing to identify the causative gene by Sanger sequencing, SNP-array, and whole-exome sequencing (WES), we finally detected a heterozygous gross deletion of PAX3 (10.26kb, chr2: 223153899-223164405) in a WS family by TGS. Our description would enrich the genetic map of WS and help us to further understand this disease. Our findings also demonstrated the value of TGS in clinical genetics researches.