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.
Keywords:
CCM3 mutation; Familial cerebral cavernous malformations; Impaired angiogenesis; Incomplete penetrance.
MeSH terms
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Amino Acid Motifs
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Amino Acid Substitution
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Apoptosis Regulatory Proteins / genetics*
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Apoptosis Regulatory Proteins / physiology
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Carrier Proteins / genetics
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Conserved Sequence
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Gait Disorders, Neurologic / etiology
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Hemangioma, Cavernous, Central Nervous System / complications
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Hemangioma, Cavernous, Central Nervous System / genetics*
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Hemangioma, Cavernous, Central Nervous System / pathology
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Humans
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KRIT1 Protein
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Magnetic Resonance Imaging
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Male
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Membrane Proteins / genetics*
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Membrane Proteins / physiology
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Microtubule-Associated Proteins / genetics
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Middle Aged
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Mutation, Missense*
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Neovascularization, Physiologic / genetics
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Pedigree
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Point Mutation*
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Polymorphism, Single Nucleotide
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / physiology
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Vision Disorders / etiology
Substances
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Apoptosis Regulatory Proteins
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CCM2 protein, human
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Carrier Proteins
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KRIT1 Protein
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KRIT1 protein, human
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Membrane Proteins
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Microtubule-Associated Proteins
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PDCD10 protein, human
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Proto-Oncogene Proteins