title: Genetic analysis of PAX3 for diagnosis of Waardenburg syndrome type I.
abstract: CONCLUSIONS
  PAX3 genetic analysis increased the diagnostic accuracy for Waardenburg syndrome type I (WS1). Analysis of the three-dimensional (3D) structure of PAX3 helped verify the pathogenicity of a missense mutation, and multiple ligation-dependent probe amplification (MLPA) analysis of PAX3 increased the sensitivity of genetic diagnosis in patients with WS1.
  
  
  OBJECTIVE
  Clinical diagnosis of WS1 is often difficult in individual patients with isolated, mild, or non-specific symptoms. The objective of the present study was to facilitate the accurate diagnosis of WS1 through genetic analysis of PAX3 and to expand the spectrum of known PAX3 mutations.
  
  
  METHODS
  In two Japanese families with WS1, we conducted a clinical evaluation of symptoms and genetic analysis, which involved direct sequencing, MLPA analysis, quantitative PCR of PAX3, and analysis of the predicted 3D structure of PAX3. The normal-hearing control group comprised 92 subjects who had normal hearing according to pure tone audiometry.
  
  
  RESULTS
  In one family, direct sequencing of PAX3 identified a heterozygous mutation, p.I59F. Analysis of PAX3 3D structures indicated that this mutation distorted the DNA-binding site of PAX3. In the other family, MLPA analysis and subsequent quantitative PCR detected a large, heterozygous deletion spanning 1759-2554 kb that eliminated 12-18 genes including a whole PAX3 gene.
authors.affiliation: Department of Otolaryngology, Laboratory of Auditory Disorders, National Institute of Sensory Organs, National Tokyo Medical Center, Japan. matsunagatatsuo@kankakuki.go.jp
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Matsunaga
authors.forename: Hideki
authors.initials: H
authors.lastname: Mutai
authors.forename: Kazunori
authors.initials: K
authors.lastname: Namba
authors.forename: Noriko
authors.initials: N
authors.lastname: Morita
authors.forename: Sawako
authors.initials: S
authors.lastname: Masuda
mesh_terms: D016022:Case-Control Studies; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007564:Japan; D008297:Male; D020125:Mutation, Missense; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D010375:Pedigree; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D014849:Waardenburg Syndrome / Q000175:diagnosis* / Q000235:genetics*
chemical_list: D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors