title: A novel deletion mutation in CCM1 gene (krit1) is detected in a Chinese family with cerebral cavernous malformations.
abstract: 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.
authors.affiliation: Key Laboratory of Biotechnology, College of Life Science, Ningxia University, Yinchuan 750021, China.
authors.forename: Bao-Hu
authors.initials: BH
authors.lastname: Ji
authors.forename: Wei
authors.initials: W
authors.lastname: Qin
authors.forename: Tao
authors.initials: T
authors.lastname: Sun
authors.forename: Guo-Yin
authors.initials: GY
authors.lastname: Feng
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.forename: Yu-Jiong
authors.initials: YJ
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D016543:Central Nervous System Neoplasms / Q000235:genetics*; D002681:China; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005838:Genotype; D020786:Hemangioma, Cavernous, Central Nervous System / Q000235:genetics*; D006801:Humans; D000075927:KRIT1 Protein; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D017384:Sequence Deletion; D055815:Young Adult
chemical_list: D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins; D004247:DNA