A novel mutation of PAX3 in a Chinese family with Waardenburgsyndrome

[摘要] Purpose: The molecular characterization of 34 members of a Chinesefamily, with 22 members in four generations, affected with Waardenburgsyndrome (WS1).Methods: A detailed family history and clinical data were collected.A genome-wide scan by two-point linkage analysis using more than 400microsatellite markers in combination with haplotype analysis wasperformed. Mutation screening was carried out in the candidate gene bysequencing of amplified products.Results: A maximum two-point lod score of 6.53 at θ=0.00 wasobtained with marker D2S2248. Haplotype analysis placed the WS1 locus toa 45.74 cM region between D2S117 and D2S206, in close proximity to thePAX3 gene on chromosome 2q35. Mutation screening in PAX3identified a 701T>C mutation which converted a highly conserved Leuto Pro. This nucleotide alteration was neither seen in unaffectedmembers of the family nor found in 50 unrelated control subjects.Conclusions: The present study identified a novel 701T>C mutationin PAX3. The mutation observed in this family highlights thephenotypic heterogeneity of the disorder.

[学科分类] 生物化学/生物物理