反常性痤疮一家系调查及致病基因突变分析

Acne inversa in a family：a clinical survey and genetic mutation analysis

目的：研究一个反常性痤疮家系患者γ分泌酶基因突变情况。方法收集1个反常性痤疮患者家系资料，该家系共4代30人，患者12例，其中在世患者9例。提取先证者及其有关亲属8例（患者5例、非患者3例）外周血DNA，采用PCR扩增NCSTN、PSEN1、PSENEN、Aph1基因编码区的全部外显子及其侧翼序列，测序并分析。选取100例健康人作为对照。结果基因检测发现，5例患者外周血DNA中的PSENEN基因发生c.229_230insCACC插入突变，导致氨基酸翻译过程中移码，不能形成功能正常的PSENEN蛋白，家系中3例正常亲属及100例健康对照均无该突变。结论反常性痤疮家系存在1个新的插入突变，即PSENEN c.229_230insCACC突变，可能是引起该家系反常性痤疮患病的分子机制。

Objective To analyze γ？secretase gene mutations in a pedigree with acne inversa. Methods Clinical data were collected from a pedigree with acne inversa, which contained 30 members spanning 4 generations. Of these members, 12 were affected by acne inversa, and 9 of the affected members were alive. Peripheral blood DNA was obtained from the proband, his seven relatives （including 4 affected and 3 unaffected members）, and 100 unrelatedhealthy human controls. PCR was performed to amplify all the coding exons and their flanking sequences of the NCSTN, PSEN1, PSENEN, Aph1 genes followed by DNA sequencing. Results A heterozygous insertion mutation （c.229_230insCACC）of the PSENEN gene, which led to translational frameshifting and resulted in dysfunciton of the PSENEN protein, was detected in all the 5 patients, but not in unaffected members or healthy controls. Conclusion There is a novel heterozygous insertion mutation c.229_230insCACC in the PSENEN gene, which may be the molecular basis of acne inversa in this family.