The incidence of deafness is non-randomly distributed among families segregating for Waardenburg syndrome type 1 (WS1)

• Published in: Journal of medical genetics Vol. 34; no. 6; pp. 447 - 452
• Main Authors: Morell, R, Friedman, T B, Asher, J H, Robbins, L G
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd 01.06.1997; BMJ; BMJ Publishing Group LTD
• Subjects: Alleles; Biological and medical sciences; Complex syndromes; Deafness - congenital; Deafness - etiology; Deafness - genetics; DNA-Binding Proteins - genetics; Female; Humans; Male; Medical genetics; Medical sciences; Mutation; Paired Box Transcription Factors; PAX3 Transcription Factor; Phenotype; Stochastic Processes; Transcription Factors; Waardenburg Syndrome - classification; Waardenburg Syndrome - complications; Waardenburg Syndrome - genetics; Human; Skin disease; Family study; Waardenburg syndrome; Gene penetrance; Auditory disorder; Clinical form; ENT disease; Mutation; Complex syndrome; Hearing loss
• ISSN: 0022-2593; 1468-6244; 1468-6244
• DOI: 10.1136/jmg.34.6.447

Waardenburg syndrome (WS) is caused by autosomal dominant mutations, and is characterised by pigmentary anomalies and various defects of neural crest derived tissues. It accounts for over 2% of congenital deafness. WS shows high variability in expressivity within families and differences in penetrance of clinical traits between families. While mutations in the gene PAX3 seem to be responsible for most, if not all, WS type 1, it is still not clear what accounts for the reduced penetrance of deafness. Stochastic events during development may be the factors that determine whether a person with a PAX3 mutation will be congenitally deaf or not. Alternatively, genetic background or non-random environmental factors or both may be significant. We compared the likelihoods for deafness in affected subjects from 24 families with reported PAX3 mutations, and in seven of the families originally described by Waardenburg. We found evidence that stochastic variation alone does not explain the differences in penetrances of deafness among WS families. Our analyses suggest that genetic background in combination with certain PAX3 alleles may be important factors in the aetiology of deafness in WS.