Detection of Novel Mutation in Ccm3 Causes Familial Cerebral Cavernous Malformations
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Cerebral cavernous malformations are vascular lesions that usually involve brain micro-vessels. They can occur both in a sporadic form and familial one. Causes of familial forms are mutations at three loci: CCM1/KRIT1, CCM2/MGC4607, and CCM3/PDCD10. Here, we describe a novel CCM3 missense mutation (c.422T>G) detected in two Greek brothers showing multiple lesions at magnetic resonance imaging; to date, only the youngest is symptomatic. Bioinformatics tools showed this novel variant causes a loss of function in Pdcd10 protein due to its localization in the eighth helix and, particularly, affects Leu141, a highly conserved amino acid. Roles of Pdcd10 in angiogenesis regulation and its association with early development of cerebral cavernous malformations were also considered.
KeywordsFamilial cerebral cavernous malformations CCM3 mutation Incomplete penetrance Impaired angiogenesis
We are thankful to Dr. Eugenia Avdellidou and Dr. Eleni Fourkala of the Department of Neurology, Hippokration General Hospital, Thessaloniki, Greece, for their contribution to this study.
- Goudreault M, D’Ambrosio LM, Kean MJ, Mullin MJ, Larsen BG, Sanchez A, Chaudhry S, Chen GI, Sicheri F, Nesvizhskii AI, Aebersold R, Raught B, Gingras AC (2009) A PP2A phosphatase high density interaction network identifies a novel striatin-interacting phosphatase and kinase complex linked to the cerebral cavernous malformation 3 (CCM3) protein. Mol Cell Proteomics 8(1):157–171PubMedCentralCrossRefPubMedGoogle Scholar
- Shenkar R, Shi C, Rebeiz T, Stockton RA, McDonald DA, Mikati AG, Zhang L, Austin C, Akers AL, Gallione CJ, Rorrer A, Gunel M, Min W, Marcondes de Souza J, Lee C, Marchuk DA, Awad IA (2014) Exceptional aggressiveness of cerebral cavernous malformation disease associated with PDCD10 mutations. Genet Med 17(3):188–196CrossRefPubMedGoogle Scholar