title: Genomic causes of multiple cerebral cavernous malformations in a Japanese population.
abstract: Cerebral cavernous malformation (CCM) is a hamartomatous vascular disease affecting the central nervous system. A fraction of CCM are thought to arise in association with genomic mutations in the cerebral cavernous malformation 1 (CCM1) (KRIT1), CCM2 (MGC4607), and CCM3 (PDCD10) genes. In the present study, 18 Japanese patients with multiple CCM (10 with familial type and eight with sporadic type), underwent genomic analysis for CCM1, CCM2 and CCM3 mutations with blood samples and surgical specimens. MRI showed CCM in the cerebral hemisphere in 17 patients, the cerebellum in 10, the brainstem in 10 and the spinal cord in eight. CCM2 mutations were the most prominent, followed by CCM1 and CCM3. CCM1, CCM2 and CCM3 mutations were not identified in seven patients. Among the 10 patients with familial CCM, CCM1, CCM2 and CCM3 mutations were found in two, three and one patient, respectively, whereas four patients lacked these mutations. Among the eight patients with sporadic CCM, these mutations were found in one, three, and one patients, respectively, whereas three patients lacked these mutations. Most of the patients had a stable course during the follow-up period. Genomic mutations other than CCM1, CCM2 and CCM3 may be frequent in patients with multiple CCM in the Japanese population.
authors.affiliation: Department of Neurological Surgery, Juntendo University Urayasu Hospital, 2-1-1 Tomioka, Urayasu, Chiba 279-0021, Japan. shotaro@juntendo-urayasu.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsutsumi
authors.forename: Ikuko
authors.initials: I
authors.lastname: Ogino
authors.forename: Masakazu
authors.initials: M
authors.lastname: Miyajima
authors.forename: Tomomi
authors.initials: T
authors.lastname: Ikeda
authors.forename: Noriko
authors.initials: N
authors.lastname: Shindo
authors.forename: Yukimasa
authors.initials: Y
authors.lastname: Yasumoto
authors.forename: Masanori
authors.initials: M
authors.lastname: Ito
authors.forename: Hajime
authors.initials: H
authors.lastname: Arai
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics; D020295:Brain Stem Neoplasms / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000473:pathology; D002528:Cerebellar Neoplasms / Q000235:genetics; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D016678:Genome; D020786:Hemangioma, Cavernous, Central Nervous System / Q000145:classification / Q000235:genetics*; D006801:Humans; D007564:Japan; D000075927:KRIT1 Protein; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013120:Spinal Cord Neoplasms / Q000235:genetics; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; C502544:CCM2 protein, human; D002352:Carrier Proteins; D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C495390:PDCD10 protein, human; D011518:Proto-Oncogene Proteins