title: Detection of Novel Mutation in Ccm3 Causes Familial Cerebral Cavernous Malformations.
abstract: 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.
authors.affiliation: Department of Biomedical Sciences and Morpho-functional Images, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, Via C. Valeria 1, 98125, Messina, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Scimone
authors.affiliation: IRCCS Centro Neurolesi "Bonino-Pulejo", Contrada Casazza, SS113, 98124, Messina, Italy.
authors.forename: Placido
authors.initials: P
authors.lastname: Bramanti
authors.affiliation: Department of Biomedical Sciences and Morpho-functional Images, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, Via C. Valeria 1, 98125, Messina, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Ruggeri
authors.affiliation: Department of Neurology, Hippokration General Hospital, 49 Konstantinoupoleos Street, Thessaloniki, Greece.
authors.forename: Zoe
authors.initials: Z
authors.lastname: Katsarou
authors.affiliation: Department of Biomedical Sciences and Morpho-functional Images, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, Via C. Valeria 1, 98125, Messina, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Donato
authors.affiliation: Department of Biomedical Sciences and Morpho-functional Images, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, Via C. Valeria 1, 98125, Messina, Italy. asidoti@unime.it.
authors.forename: Antonina
authors.initials: A
authors.lastname: Sidoti
authors.affiliation: Department of Biomedical Sciences and Morpho-functional Images, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, Via C. Valeria 1, 98125, Messina, Italy.
authors.forename: Rosalia
authors.initials: R
authors.lastname: D'Angelo
mesh_terms: D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics; D017124:Conserved Sequence; D020233:Gait Disorders, Neurologic / Q000209:etiology; D020786:Hemangioma, Cavernous, Central Nervous System / Q000150:complications / Q000235:genetics* / Q000473:pathology; D006801:Humans; D000075927:KRIT1 Protein; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008875:Middle Aged; D020125:Mutation, Missense; D018919:Neovascularization, Physiologic / Q000235:genetics; D010375:Pedigree; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D014786:Vision Disorders / Q000209:etiology
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
keywords: CCM3 mutation; Familial cerebral cavernous malformations; Impaired angiogenesis; Incomplete penetrance