De Novo MGC4607 Gene Heterozygous Missense Variants in a Child with Multiple Cerebral Cavernous Malformations

• Published in: Journal of molecular neuroscience Vol. 47; no. 3; pp. 475 - 480
• Main Authors: Mosca, Lorena, Pileggi, Silvana, Avemaria, Francesca, Tarlarini, Claudia, Cigoli, Maria Sole, Capra, Valeria, De Marco, Patrizia, Pavanello, Marco, Marocchi, Alessandro, Penco, Silvana
• Format: Journal Article
• Language: English
• Published: New York Humana Press Inc 01.07.2012; Springer Nature B.V
• Subjects: Automation; Biomedical and Life Sciences; Biomedicine; Cell Biology; Central Nervous System Neoplasms - genetics; Child; Convulsions & seizures; DNA; DNA sequencing; Epilepsy; Exons; Family medical history; Female; Genes; Genetic Carrier Screening; Genetic testing; Genetic Variation - genetics; Hemangioma, Cavernous, Central Nervous System - genetics; Hemorrhage; Humans; Kinases; Male; Mutation; Mutation, Missense - genetics; Nervous system; Neurochemistry; Neurological diseases; Neurology; Neurosciences; Pedigree; Point mutation; Proteins; Proteomics; Seizures; Cerebral cavernous malformations; CCM2; gene; De novo mutation
• ISSN: 0895-8696; 1559-1166; 1559-1166
• DOI: 10.1007/s12031-012-9741-5

Cavernous malformations are angiographically occult, low-pressure neurovascular lesions with distinct imaging and clinical characteristics; main clinical manifestations are seizure, focal neurological deficits and epileptic attacks. Here we describe the molecular characterization of an Italian child, a symptomatic patient, affected by multiple cerebral cavernous malformations, without a family history of the disease and harbouring a new MGC4607 gene mutation. We identified two de novo missense variants in exon 6 of the gene both present on the same allele ( cis configuration). DNA analysis for KRIT1 , and PDCD10 gene variation through direct sequencing and MLPA analysis excluded further mutations. STR multiplex assay, allele-specific analysis and DHPLC analysis were performed for a better genetic characterization. Our findings emphasize the importance of the genetic test in subjects presenting multiple cerebral cavernomas for an adequate counselling, as well as for disease management since early identification of genetic abnormalities enable patients to have their lesions removed before they haemorrhage and cause deficit and/or epilepsy.