Yang J-Q, Wu X-J, Dou T-T, Jiao T, Chen X-B, Min M, Cai S-Q, Zheng M
Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Dermatology, First Affiliated Hospital of Huzhou University, Huzhou, China.
Clin Exp Dermatol. 2015 Dec;40(8):916-9. doi: 10.1111/ced.12724. Epub 2015 Jul 30.
Hidradenitis suppurativa (HS) is a chronic disease of follicular occlusion. It involves the axilla, groin, perianal and perineal regions, and is characterized by recurrent draining sinuses, skin abscesses and disfiguring scars. Loss-of-function mutations in the genes encoding γ-secretase have been identified as a cause of HS. We collected skin samples from three patients with HS from a Chinese family carrying a NCSTN mutation (c.1258C>T (p.Q420X)) and three unrelated healthy controls (HCs). Expression level of nicastrin in skin tissue and cultured keratinocytes and fibroblasts of patients and HCs was determined by real-time quantitative PCR and western blotting. We found that the mRNA and protein levels of nicastrin were significantly reduced in the whole skin, epidermis, dermis, and cultured keratinocytes and fibroblasts compared with HCs. Therefore, we conclude that haploinsufficiency of the NCSTN gene caused by the nonsense mutation c.1258C>T (p.Q420X) contributes to the occurrence of HS in this family.
化脓性汗腺炎（HS）是一种毛囊闭塞的慢性疾病。它累及腋窝、腹股沟、肛周和会阴区域，其特征为反复出现引流性窦道、皮肤脓肿和毁容性瘢痕。编码γ-分泌酶的基因突变功能丧失已被确定为HS的一个病因。我们从一个携带NCSTN突变（c.1258C>T（p.Q420X））的中国家族的三名HS患者以及三名无关健康对照（HC）中收集了皮肤样本。通过实时定量PCR和蛋白质免疫印迹法测定患者和HC皮肤组织、培养的角质形成细胞和成纤维细胞中尼卡斯特林的表达水平。我们发现，与HC相比，尼卡斯特林的mRNA和蛋白质水平在全皮肤、表皮、真皮以及培养的角质形成细胞和成纤维细胞中均显著降低。因此，我们得出结论，由无义突变c.1258C>T（p.Q420X）导致的NCSTN基因单倍体不足促成了该家族中HS的发生。
