SCCD的发病机理及其致病基因UBIAD1的功能研究进展

Functional research progress of UBIAD1 and pathogenesis of SCCD

施奈德结晶状角膜营养不良(SCCD)是一种稀有的常染色体显性遗传病,其发病的分子基础为UBIAD1基因突变,致病机理为UBIAD1基因突变后,UBIAD1蛋白构象发生改变而不能与GGpp化合物结合,导致UBIAD1-HMG CoA还原酶复合体无法分离,HMG CoA还原酶不能从内质网膜解离至细胞质被蛋白酶体识别和降解,从而导致胆固醇和非甾醇类异戊二烯化合物在细胞中合成并积累。本文综述了SCCD的临床表现、分子基础及其致病基因UBIAD1的功能,以期为SCCD的分子诊断和治疗提供参考,为阐明UBIAD1基因的功能奠定基础。

·The molecular basis of schnyder crystalline corneal dystrophy(SCCD)is UBIAD1 gene mutation.The pathogenesis of SCCD includes conformational change of UBIAD1 protein which leads to loss of combination with GGpp compounds.UBIAD1-HMG CoA reductase complexes can’t be separated,and the rate-limiting enzyme can’t dissociate from endoplasmic reticulum to cytoplasm,which results in loss of recognition and degradation by the proteasome.The direct consequence is the gradual accumulation and biosynthesis of cholesterol and non-sterol isoprenoids compounds in the cell.This paper reviews the clinical manifestation,molecular basis,pathogenesis of SCCD and the function of UBIAD1 which provide guidance for molecular diagnosis and treatment of SCCD and pave the way for elucidating the function of UBIAD1 in vivo.