痣样基底细胞癌综合征一家系PTCH1基因突变分析

目的 对痣样基底细胞癌综合征一家系进行PTCH1基因突变分析。 方法 提取先证者（Ⅱ5）及Ⅱ1、Ⅱ3、Ⅲ4的DNA，以50例健康人为对照。应用聚合酶链反应（PCR）、DNA直接测序明确突变位点，根据突变位点设计特异性引物，用PCR来检测突变位点从而进一步确定该家系的致病原因。 结果 先证者PTCH1基因的1条等位基因第14号外显子上2137位胞嘧啶C被胸腺嘧啶T替代（c.2137C > T），即CAG→TAG，导致终止密码产生（Q714X），Ⅲ4也检测到相同突变。健康对照者中未检出该突变。 结论 PTCH1基因的无义突变（c.2137C > T）可能是引起该患者临床症状的特异性突变。

Mutation analysis of the PTCH1 gene in a pedigree with nevoid basal cell carcinoma syndrome

Gao Di, Huang Ershun, Sun Tingting, Yan Huimin, You Yanming, Jiang Wei. Department of Dermatology, Peking University Third Hospital, Beijing 100191, China Corresponding author: Jiang Wei, Email: jiangwei@medmail.com.cn 【Abstract】 Objective To analyze mutations in the PTCH1 gene in a pedigree with nevoid basal cell carcinoma syndrome （NBCCS）. Methods Blood samples were collected from a 58-year-old male proband with NBCCS （Ⅱ5）, his brothers （Ⅱ1 and Ⅱ3） and son （Ⅲ4）, and 50 unrelated healthy human controls. DNA was extracted from these blood samples. PCR and direct DNA sequencing were performed to determine mutation sites in the PTCH1 gene. According to the mutation sites, allele-specific oligonucleotide primers were designed and used to confirm the pathogenic mutations in this pedigree through PCR. Results A nonsense mutation （c.2137C）, which leads to the substitution of CAG by TAG with the generation of a premature termination codon （Q714X）, was identified in exon 14 in one allele of the PTCH1 gene in the proband and his son, but in none of the healthy human controls. Conclusion The nonsense mutation （c.2137C > T） in the PTCH1 gene may be a specific mutation causing the clinical symptoms in the patient with NBCCS.