Genetic analysis of PAX3 for diagnosis of Waardenburg syndrome type I.
Acta Otolaryngol
; 133(4): 345-51, 2013 Apr.
Article
in En
| MEDLINE
| ID: mdl-23163891
ABSTRACT
CONCLUSION:
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.OBJECTIVES:
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Waardenburg Syndrome
/
Genetic Predisposition to Disease
/
Paired Box Transcription Factors
Type of study:
Diagnostic_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Country/Region as subject:
Asia
Language:
En
Journal:
Acta Otolaryngol
Year:
2013
Document type:
Article
Affiliation country:
Japan