CAJ | 학술논문

脑海绵状血管瘤(CCM)是多定位于中枢神经系统的一种脑部血管异常,少数在皮肤和视网膜处有并发症.依据致病基因在染色体上的不同位置分为CCM1、CCM2和CCM3 3种类型.目前,CCM1、CCM2和CCM3的致病基因已经被克隆,分别为hrit1、MGC4607和细胞程序性死亡10基因(PDCD10).利用连锁分析发现内蒙古的一个家系属于CCM1,突变检测发现患者CCM1基因(krit1)第9内含子和第10外显子拼接位点处存在一"GTA"缺失,该突变导致终止密码子提前出现,产生截短蛋白.实验结果支持krit1为CCM1致病基因.
뇌해면상혈관류(CCM)시다정위우중추신경계통적일충뇌부혈관이상,소수재피부화시망막처유병발증.의거치병기인재염색체상적불동위치분위CCM1、CCM2화CCM3 3충류형.목전,CCM1、CCM2화CCM3적치병기인이경피극륭,분별위hrit1、MGC4607화세포정서성사망10기인(PDCD10).이용련쇄분석발현내몽고적일개가계속우CCM1,돌변검측발현환자CCM1기인(krit1)제9내함자화제10외현자병접위점처존재일"GTA"결실,해돌변도치종지밀마자제전출현,산생절단단백.실험결과지지krit1위CCM1치병기인.
Cerebral Cavernous Malformations (CCM) are vascular malformations that are mostly located in the central nervous system (CNS) and occasionally within the skin and retina, which are classified into three types (CCM1, CCM2 and CCM3) by being located at different loci on chromosomes. At present, CCM1 (7q21), CCM2 (7p13-p15) and CCM3 (3q25.2-q27) are respectively linked to krit1 (Krev interaction trapped gene 1), MGC4607 and PDCD10 (programmed cell death 10). In this work, we identified a novel "GTA" deletion mutation at the acceptor splicing site of intron9/exon10 on krit1. The mutation results in an abnormally spliced protein by creating a premature termination code at the 23rd amino acid downstream from the sequence alteration.Our results are consistent with previous research on krit1 mutations and confirm the conclusion that KRIT1 haploinsufficiency may be the underlying mechanism of CCM1.