Abstract
Cerebral cavernous malformations (CCMs) are congenital vascular anomalies of the central nervous system that can result in seizures, haemorrhage, recurrent headaches and focal neurologic deficit. CCMs can occur as an autosomal dominant trait with incomplete penetrance and a wide phenotypic variability. The genes responsible for this disease are KRIT1/CCM1 on chromosome 7q21.2, MGC4607/CCM2 on chromosome 7p15–p13 and PDCD10/CCM3 on chromosome 3q25.2–q27. Mutations in KRIT1/CCM1 account for more than 40% of CCMs. We previously reported a CCM family harbouring the KRIT1/CCM1 1204delAACAA mutation. In order to search for possible explanation of the clinical variability observed, we looked for genetic variation within exons and exon/intron regions in the three genes KRIT1, MGC4607 and PDCD10 associated to the disease within this large family, 23 subjects have been analysed. Identified genetic variations in the three genes are here presented. We believe that genetic variations could interfere with the proper CCM1/CCM2/CCM3 protein complex thus explaining the observed clinical variability.
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Acknowledgments
The authors thank LICE (Lega Italiana Contro l'Epilessia) for the contribution to this study.
Author Contributions
Study concept and design: Silvana Penco
Acquisition of data: Silvana Pileggi and Serena Buscone
Analysis and interpretation of data: Silvana Penco, Silvana Pileggi, Alessandro Marocchi and Stefania Battistini
Drafting the manuscript: Silvana Penco and Silvana Pileggi
Administrative, technical and material support: Stefania Battistini, Claudia Ricci, Paola Brunori, Maria Cristina Patrosso and Silvana Penco
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DHPLC conditions for each amplicon of the three genes (DOC 87 kb)
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Pileggi, S., Buscone, S., Ricci, C. et al. Genetic Variations Within KRIT1/CCM1, MGC4607/CCM2 and PDCD10/CCM3 in a Large Italian Family Harbouring a Krit1/CCM1 Mutation. J Mol Neurosci 42, 235–242 (2010). https://doi.org/10.1007/s12031-010-9360-y
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DOI: https://doi.org/10.1007/s12031-010-9360-y