反常性痤疮一家系临床表型及基因突变研究

Clinical and genetic analysis of a pedigree with acne inversa

目的 研究1个反常性痤疮患者家系的基因突变.方法 对一确诊的反常性痤疮先证者家系进行现场调查,并采集外周血标本.PCR扩增早老素1（PSEN1）、单过性跨膜蛋白（NCSTN）和早老素增强子2（PSENEN）的所有外显子,PCR产物进行序列分析.结果 该家系共有5代67人,其中25人患病（男13例,女12例）,符合常染色体显性遗传.家系中患者皮损主要分布于颈背部、胸部和臀部,腋下很少或未被累及.家系中11例患者NCSTN基因第11号外显子存在c.1258C＞T错义突变,导致第420位由氨基酸谷氨酰胺变为终止密码子.同时检测家系中6例无反常性痤疮的正常人及与该家系无关的100名健康对照者,未发现该突变.检索美国国家生物技术信息中心（NCBI）网站单核苷酸多态性（SNP）数据库,未发现该突变.结论 该反常性痤疮家系存在一个新的错义突变,即NCSTN基因1 1号外显子c.1258C＞T,这可能是该家系患者发病的分子基础.

Objective To detect γ-secretase gene mutations in a large Chinese pedigree with acne inversa （AI）.Methods Clinical evaluation was carried out in a large pedigree with AI through field investigation.Peripheral blood samples were obtained from 17 family members （11 affected and 6 unaffected） and 100 unrelated healthy human controls.DNA was extracted from the blood samples,and PCR was performed to amplify all the coding regions of PSEN 1,PSENEN and NCSTN genes followed by DNA sequencing analysis.Results There were 67 members over 5 generations in this family,of whom,25 （13 males and 12 females） were affected by AI.AI was inherited in an autosomal dominant manner in this family.Skin lesions were mainly distributed on the neck,back,chest and buttocks,and occasionally in subaxillary regions.DNA sequencing revealed a novel missense mutation,c.1258C〉 T （p.Q420XP）,in the exon 11 of the NCSTN gene in 11 affected family members,which leads to a substitution of glutamine by a premature termination codon at amino acid 420 （p.Q420X）.The mutation was undetected in either the unaffected members or the unrelated healthy controls,and had not been registered in the single nucleotide polymorphism （SNP） database in National Center for Biotechnology Information.Conclusions There is a novel heterozygous missense mutation,c.1258C 〉 T in the exon 11 of the NCSTN gene,which may be the molecular basis of pathogenesis of AI in this family.