The Novel Mevalonate Kinase Mutations Cause Disseminated Superficial Actinic Porokeratosis
The Novel Mevalonate Kinase Mutations Cause Disseminated Superficial Actinic Porokeratosis
复制标题
新型甲羟戊酸激酶突变导致播散性浅表光化性汗孔角化病
DOI：
--
复制
发表时间：
2018
影响因子：
10.3
通讯作者：
J. Tan
中科院分区：
文献类型：
--
作者：
T. Zhu1;D. Tian;L. Zhang;X. Xu;K. Xia;Z. Hu;Z. Xiong;J. Tan
Disseminated superficial actinic porokeratosis (DSAP) is a rare autosomal dominant disease. In our previous research, we found that a linkage region of DSAP in a large family is located at 12q23.2‐q24.1. Subsequently, mevalonate kinase (MVK) gene was proved as a pathogenic gene of DSAP. Here, we report a new missense mutation c.566 C> T (p.A189V) in MVK in a Chinese DSAP pedigree. Mechanically, we demonstrate that both pathogenic p.A189V mutant and a sporadic mutation p.H312R(c.935A>G) which we reported previously have rapid degradation, decreased kinase activity and reduced production of cell cholesterol. Meanwhile, we found p.H312R mutation make MVK inability to form dimers. Furthermore, we demonstrate that the mutants are impaired in mitochondrial function and lead to increased apoptosis. Our results provide an important basis for elucidating the mechanism by which MVK missense mutations contribute to DSAP.
