摘要BACKGROUND: A cerebral cavernous malformation-1 (CCM1) gene mutation might result in functional loss of KREV interaction trapped-1 (KRIT1), which is related to onset of cavernous malformations (CM). However, data addressing sporadic CM in Chinese patients remains limited to date.OBJECTIVE: To analyze CCM1 mutation of Chinese patients with sporadic intracranial CM.DESIGN, TIME AND SETTING: Genetics experiment was performed in the Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University between January 2004 and December 2005.PARTICIPANTS: Ninety patients with sporadic CM served as the CM group, and 30 healthy subjects were considered to be the control group.METHODS: Peripheral blood was collected from patients with CM and from control group subjects.Genomic DNA was extracted, and exons 8, 9, 11, 12, 13, 15, 16, 17, and 18, as well as the related introns, were amplified using polymerase chain reaction. DNA sequences were compared with GeneBank.MAIN OUTCOME MEASURES: Abnormal mutable site of CCM1 gene in the two groups.RESULTS: Four exclusive mutations of CCM1 were detected in the CM group, with a sporadic CM mutational rate of 32% (6/19). Of the four exclusive mutations, there was one missense mutation [exon 12, 1172C→T (S391F)], one insertion mutation [exon 8, 704insT (K246stop)], one intervening sequence mutation (IVS12-4C→T), and one synonymous mutation (exon 17,1875C→T). With the exception of 1875C→T, all mutations detected in the CM group led to functional changes of the KRIT1 protein, which was encoded by the CCM1 gene. Gene mutations were not detected in the control group.CONCLUSION: Four exclusive mutations of the CCM1 gene were determined in Chinese patients with sporadic CM, which led to functional changes or loss of the encoding KRIT1 protein. KRIT1 protein is considered to be the genetic basis of CM occurrence.