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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?
Author(s) -
Tekin M,
Bodurtha JN,
Nance WE,
Pandya A
Publication year - 2001
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1034/j.1399-0004.2001.600408.x
Subject(s) - waardenburg syndrome , pax3 , genetics , loss of heterozygosity , missense mutation , compound heterozygosity , biology , mutation , phenotype , gene , allele , transcription factor
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.