中文摘要：

目的 研究一家系2例汉族反常性痤疮患者γ分泌酶基因的突变。 方法 提取家系中5名成员（2例患者、先证者父亲、2例目前未发病者）的外周血DNA，扩增nicastrin蛋白（NCSTN）、早老素（PSEN） 1、早老素增强子（PSENEN）、前咽缺陷蛋白（APH1）基因所有外显子和侧翼序列进行测序，并以100例无关系健康人作为对照。同时比较先证者皮损与4个健康对照NCSTN基因mRNA表达差异。 结果 检测到2例患者血样DNA存在NCSTN基因中第477位碱基发生C→A的杂合突变，即c.477C〉A，其余3名家系成员及健康对照未发现相应突变；查询美国国家生物技术信息中心网站单核苷酸多态性数据库也未发现此突变。另外，先证者皮损NCSTN mRNA水平较健康对照明显减少。 结论 NCSTN基因新的无义突变c.477C〉A是该反常性痤疮家系的致病突变，并可能通过无义介导的mRNA降解途径导致该基因功能失活。

英文摘要：

Objective To identify mutations of the γ-secretase gene in two patients with acne inversa （AI） in a Chinese pedigree. Methods Blood samples were obtained from 5 family members （including 2 patients, the proband′s father, 2 unaffected family members） and 100 unrelated healthy controls. Genomic DNA was extracted from these blood samples, and PCR was conducted to amplify all the exons and their flanking sequences of nicastrin （NCSTN）, presenilin-1 （PSEN1）, presenilin enhancer （PSENEN） and anterior pharynx-defective 1 （APH1） genes, followed by direct sequencing. Besides, the NCSTN mRNA in skin lesions of the proband was compared with that in the normal skin of 4 healthy controls. Results A heterozygous mutation （c.477C 〉 A） at position 477 in the exon 5 of the NCSTN gene, which had not been described previously in the National Center for Biotechnology Information （NCBI） single nucleotide polymorphism database, was identified in the 2 patients, but not observed in the other 3 unaffected family members or the 100 unrelated controls. Additionally, the mRNA of NCSTN was evidently decreased in the lesions of the proband compared with the normal skin of healthy controls. Conclusion The novel nonsense mutation c.477C〉 A in the NCSTN gene is the causative mutation of AI in this family, and it may induce functional inactivation of NCSTN through the nonsense-mediated mRNA decay.