Abstract
Klein-Waardenburg syndrome or Waardenburg syndrome type 3 (WS-III; MIM 148820) is characterized by the presence of musculoskeletal abnormalities in association with clinical features of Waardenburg syndrome type 1 (WS-I). Since the description of the first patient in 1947 (D. Klein, Arch Klaus Stift Vererb Forsch 1947: 22: 336-342), a few cases have been reported. Only occasional families have demonstrated autosomal-dominant inheritance of WS-III. In a previous report, a missense mutation in the paired domain of the PAX3 gene has been described in a family with dominant segregation of WS-III. In this report, we present a second family (mother and son) with typical clinical findings of WS-III segregating with a heterozygous 13-bp deletion in the paired domain of the PAX3 gene. Although homozygosity or compound heterozygosity has also been documented in patients with severe limb involvement, a consistent genotype - phenotype correlation for limb abnormalities associated with heterozygous PAX3 mutations has not previously been apparent. Heterozygous mutations could either reflect a unique dominant-negative effect or possibly the contribution of other unlinked genetic modifiers in determining the phenotype.
Original language | English (US) |
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Pages (from-to) | 301-304 |
Number of pages | 4 |
Journal | Clinical Genetics |
Volume | 60 |
Issue number | 4 |
DOIs | |
State | Published - 2001 |
Externally published | Yes |
Keywords
- Deafness
- Klein
- Limb abnormalities
- PAX3 gene
- Waardenburg syndrome
ASJC Scopus subject areas
- Genetics
- Genetics(clinical)