title: [Analysis of CCM1 gene mutations in Chinese patients with intracranial cavernous malformations].
abstract: OBJECTIVE
  To study the CCM1 gene (7q11.2 - q22) mutations in Chinese patients with intracranial cavernous malformations (ICM), METHODS: Peripheral blood samples were collected from 25 unrelated patients with ICM confirmed by post-operational pathology, 7 being with familial ICM, all of Han nationality, and from 30 healthy people as controls. The genomic DNA was extracted and the exons 8, 9, 11, 12, 13, 15, 16, 17, and 18 of CCM1 gene and part of intervening sequences near both sides of these exons were amplified by PCR. The PCR products were sequenced directly and then compared with the GenBank data.
  
  
  RESULTS
  Seven new mutation sites of CCM1 gene were detected from 11 Chinese ICM patients with a total mutation rate of 44%. Of the seven new mutations there were three missense mutations: 1160A-->C (Q387P) and 1172C-->T (S391F) in exon12, and 1405A-->C (N469H) in exon13; two insertion mutations: 704insT (K246stop) in exon8, and 2138insG (T733stop) in exon18; one intervening sequence mutation: IVS12 - 4C-->T; and one synonymous mutation: 1875C-->T (F625F) in exon17. None mutation was detected in the control group. The CCM1 mutation rate of familial ICM was 85.7%, significantly higher than that of sporadic ICM (27.7%, P < 0.05).
  
  
  CONCLUSIONS
  As the genetic basis of ICM, CCM1 gene mutation exists in Chinese ICM patients too, that leads to functional loss or changes of the gene encoding KRIT1 protein.
authors.affiliation: Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Xie
authors.forename: Xian-cheng
authors.initials: XC
authors.lastname: Chen
authors.forename: Yong-feng
authors.initials: YF
authors.lastname: Fan
authors.forename: Ying
authors.initials: Y
authors.lastname: Xia
authors.forename: Liang
authors.initials: L
authors.lastname: Gao
authors.forename: Xiao-mu
authors.initials: XM
authors.lastname: Li
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D005260:Female; D020786:Hemangioma, Cavernous, Central Nervous System / Q000235:genetics*; D006801:Humans; D000075927:KRIT1 Protein; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D017354:Point Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*
chemical_list: D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins