常染色体显性Waardenburg综合征1家系基因突变分析

【摘要】 目的 报道1个常染色体显性Waardenburg综合征家系,检测并分析其致病基因。方法 收集1个中国汉族常染色体显性Waardenburg综合征家系,采集先证者及其父母临床资料和外周血,提取DNA,应用二代皮肤靶向测序包检测患者突变基因,Sanger测序验证确定致病基因。结果 先证者表现为腹部、下肢不规则白斑,右耳中重度感音神经性耳聋,双眼虹膜异色,其母亲双眼虹膜异色,内眦赘皮,早白发,眉毛粗浓,该家系中先证者及其母亲均诊断为Waardenburg综合征,且两者 PAX3基因7号外显子编码区第976-977位AG均被替换为T,导致PAX3蛋白从第327位氨基酸开始发生移码（第327位氨基酸由苏氨酸转变为脯氨酸）,到第54位氨基酸位置时终止［c.976-977delinsT（p.Thr327Profs*54）］;患儿父亲未患病,基因检测正常。结论 PAX3基因移码突变c.976-977delinsT（p.Thr327Profs*54） 为新发现的突变,可能为引起该家系患者临床表型的致病基因。

Gene mutation analysis in a Chinese pedigree with autosomal dominant Waardenburg syndrome

【Abstract】 Objective To report a Chinese pedigree with autosomal dominant Waardenburg syndrome, and to identify causative gene mutations. Methods Clinical data and peripheral blood samples were collected from the proband and her parents. Genomic DNA was extracted, gene mutations were detected through a next?generation skin?targeted sequencing panel, and Sanger sequencing was performed to verify causative mutations. Results The proband clinically presented with irregular white patches on the abdomen and lower limbs, moderate to severe sensorineural deafness in the right ear, and iris heterochromia in both eyes. The proband′s mother presented with iris heterochromia in both eyes, epicanthus, early canities and thick eyebrows. In the family, both the proband and her mother were diagnosed with Waardenburg syndrome. A causative frameshift mutation c.976?977delinsT（p.Thr327Profs*54） was identified in both the proband and her mother, which caused the AG to TT base substitution at positions 976 - 977 in the coding region of exon 7 of the PAX3 gene, resulted in a frameshift from the amino acid position 327 to 54 in the PAX3 protein （threonine was substituted by proline at amino acid position 327）. The proband′s father showed a normal phenotype, and his genetic test results were negative. Conclusion The novel frameshift mutation c.976?977delinsT （p.Thr327Profs*54） in the PAX3 gene may contribute to the clinical phenotype of the patients with Waardenburg syndrome in the family.