多发性家族性毛发上皮瘤致病基因的确定

目的 对多发性家族性毛发上皮瘤一家系进行基因定位及候选基因突变检测。方法 共用18对覆盖9p21和16q12-q13的微卫星标记对一个多发性家族性毛发上皮瘤家系进行局部基因组扫描,并用Linkage软件进行两点参数连锁分析,最后PCR扩增CYLD1基因的17个编码外显子及其邻近剪接子并进行双向直接测序。结果 ①两点参数连锁分析在常染色体显性遗传模式下,外显率为99.9%、基因频率0.00001时在D16S3068位点处得出LOD值=3.31(θ=0.00),排除与9号染色体连锁;②突变分析在CYLD1基因第18号外显子出现连续的4个碱基缺失,即c.2355-2358delCAGA。结论 多发性家族性毛发上皮瘤存在着遗传异质性,本家系的致病基因位于16q12-q13,而不在9p21。

Identification of the Disease Gene of Multiple Familial Trichoepithelioma

Objective To map the locus of the gene CYLD1 for multiple familial trichoepithelioma (MFT), and identify the mutation of this gene in a large Chinese Han family with MFT. Methods The local genome scan was performed using 18 microsatellite markers spanning 9p21 and 16q12-q13 in this MFT family. Linkage software was used for two-point linkage analysis. All 17 coding exons of the CYLD1 gene and the adjacent splice sites were amplified using PCR. Mutation scanning was carried out by DNA sequencing. Results ① Two-point linkage analysis revealed a LOD score of 3.31 under the assumption of an autosomal dominant inheritance with disease-allele frequency of 0.00001 and penetrance of 99.9%. ② A four-basepair deletion of exon 18 in the CYLD1 gene was detected, designated c.2355-2358delCAGA. Conclusions Multiple familial trichoepithelioma is a genetically heterogeneous disorder. The gene CYLD1 for this MFT family localizes to 16q12-q13, not 9p21.