Waardenburg syndrome type 3 (Klein-Waardenburg syndrome) segregating with a heterozygous deletion in the paired box domain of PAX3: a simple variant or a true syndrome?

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.

• Authors: M Tekin, J N Bodurtha, W E Nance, A Pandya
• Journal: Clinical genetics (Clin Genet) Vol. 60 Issue 4 Pg. 301-4 (Oct 2001) ISSN: 0009-9163 [Print] Denmark
• PMID: 11683776 (Publication Type: Case Reports, Journal Article)

Chemical References

• DNA-Binding Proteins
• PAX3 Transcription Factor
• PAX3 protein, human
• Paired Box Transcription Factors
• Transcription Factors
• Pax3 protein, mouse

Topics

• Chromosome Segregation (genetics)
• DNA Mutational Analysis
• DNA-Binding Proteins (chemistry, genetics)
• Exons (genetics)
• Female
• Genes, Dominant (genetics)
• Genetic Variation (genetics)
• Heterozygote
• Humans
• Infant
• Infant, Newborn
• Male
• PAX3 Transcription Factor
• Paired Box Transcription Factors
• Pedigree
• Phenotype
• Polymorphism, Single-Stranded Conformational
• Protein Structure, Tertiary
• Sequence Deletion (genetics)
• Transcription Factors
• Waardenburg Syndrome (genetics)