Ji Bao-Hu, Qin Wei, Sun Tao, Feng Guo-Yin, He Lin, Wang Yu-Jiong
Key Laboratory of Biotechnology, College of Life Science, Ningxia University, Yinchuan 750021, China.
Yi Chuan Xue Bao. 2006 Feb;33(2):105-10. doi: 10.1016/S0379-4172(06)60028-0.
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.
脑海绵状血管畸形（CCM）是一种血管畸形，主要位于中枢神经系统（CNS），偶尔也见于皮肤和视网膜，根据其在染色体上的不同位置分为三种类型（CCM1、CCM2和CCM3）。目前，CCM1（7q21）、CCM2（7p13 - p15）和CCM3（3q25.2 - q27）分别与krit1（Krev相互作用捕获基因1）、MGC4607和PDCD10（程序性细胞死亡10）相关。在这项研究中，我们在krit1基因内含子9/外显子10的受体剪接位点发现了一种新的“GTA”缺失突变。该突变通过在序列改变下游第23个氨基酸处产生一个提前终止密码子，导致异常剪接的蛋白质。我们的结果与之前关于krit1突变的研究一致，并证实了KRIT1单倍体不足可能是CCM1潜在机制的结论。
