A novel mutation of PAX3 in a Chinese family with Waardenburg syndrome.
OBJECTIVE
The molecular characterization of 34 members of a Chinese family, with 22 members in four generations, affected with Waardenburg syndrome (WS1).


METHODS
A detailed family history and clinical data were collected. A genome-wide scan by two-point linkage analysis using more than 400 microsatellite markers in combination with haplotype analysis was performed. Mutation screening was carried out in the candidate gene by sequencing of amplified products.


RESULTS
A maximum two-point lod score of 6.53 at theta = 0.00 was obtained with marker D2S2248. Haplotype analysis placed the WS1 locus to a 45.74 cM region between D2S117 and D2S206, in close proximity to the PAX3 gene on chromosome 2q35. Mutation screening in PAX3 identified a 701T > C mutation which converted a highly conserved Leu to Pro. This nucleotide alteration was neither seen in unaffected members of the family nor found in 50 unrelated control subjects.


CONCLUSIONS
The present study identified a novel 701T > C mutation in PAX3. The mutation observed in this family highlights the phenotypic heterogeneity of the disorder.
Qin
Wei
W
Bio-X Center, Shanghai Jiao Tong University, Shanghai, China.
Shu
Anli
A
Qian
Xueqing
X
Gao
Jianjun
J
Xing
Qinghe
Q
Zhang
Juan
J
Zheng
Yonglan
Y
Li
Xingwang
X
Li
Sheng
S
Feng
Guoyin
G
He
Lin
L
D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics*; D002675:Child, Preschool; D002889:Chromosomes, Human, Pair 2; D003596:Cytosine; D004252:DNA Mutational Analysis; D005260:Female; D008040:Genetic Linkage; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D007930:Leucine; D008126:Lod Score; D008297:Male; D009154:Mutation; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D011392:Proline; D013941:Thymine; D014849:Waardenburg Syndrome / Q000235:genetics*
D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D003596:Cytosine; D011392:Proline; D007930:Leucine; D013941:Thymine