PAX3 mutations and clinical characteristics in Chinese patients with Waardenburg syndrome type 1

[摘要] Purpose: To detect paired box gene 3 (PAX3)mutations and associated phenotypes in Chinese patients withWaardenburg syndrome type 1 (WS1). Methods: Five unrelated families withsuspected WS1 were selected from our Genomic DNA Repository forHereditary Eye Diseases. The coding and adjacent intronic regions of PAX3were amplified by polymerase chain reaction and the amplicons were thenanalyzed by cycle sequencing. Variations detected were furtherevaluated in available family members as well as one hundred controlswith heteroduplex-single strand conformational polymorphism(heteroduplex-SSCP) analysis and/or clone sequencing. Results: Three novel and two knownmutations in PAX3 were detected in five patients, respectively:c.567_586+17del (p.Asp189_Gln505delinsGluGlyGlyAlaLeuAlaGly),c.456_459dupTTCC (p.Ile154PhefsX162), c.795_800delCTGGTT(p.Trp266_Phe267del), c.799T>A (p.Phe267Ile), and c.667C>T(p.Arg223X). Two novel mutations proved to be de novo as their parentsdid not carry the mutations. All five patients with PAX3mutations had dystopia canthorum and different iris color and fundibetween their two eyes. However, none had white forelock, skinhypopigmentation, and deafness. Conclusions: Our findings expand thefrequency and spectrum of PAX3 mutations and ethnic-relatedphenotypes in Chinese patients with WS1. De novo mutations in PAX3have not been reported before.

[学科分类] 生物化学/生物物理