Qin Wei, Shu Anli, Qian Xueqing, Gao Jianjun, Xing Qinghe, Zhang Juan, Zheng Yonglan, Li Xingwang, Li Sheng, Feng Guoyin, He Lin
Bio-X Center, Shanghai Jiao Tong University, Shanghai, China.
Mol Vis. 2006 Aug 28;12:1001-8.
The molecular characterization of 34 members of a Chinese family, with 22 members in four generations, affected with Waardenburg syndrome (WS1).
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.
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.
The present study identified a novel 701T > C mutation in PAX3. The mutation observed in this family highlights the phenotypic heterogeneity of the disorder.
对一个中国家系中的34名成员进行分子特征分析，该家系四代中有22名成员患有瓦登伯革氏综合征（WS1）。
收集详细的家族史和临床数据。使用400多个微卫星标记通过两点连锁分析结合单倍型分析进行全基因组扫描。通过对扩增产物进行测序在候选基因中进行突变筛查。
标记D2S2248在θ = 0.00时获得的最大两点连锁lod分数为6.53。单倍型分析将WS1基因座定位到D2S117和D2S206之间45.74 cM的区域，紧邻2号染色体q35上的PAX3基因。PAX3中的突变筛查鉴定出一个701T > C突变，该突变将高度保守的亮氨酸转变为脯氨酸。这种核苷酸改变在该家系的未患病成员中未观察到，在50名无关对照受试者中也未发现。
本研究在PAX3中鉴定出一个新的701T > C突变。在这个家系中观察到的突变突出了该疾病的表型异质性。
