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Journal of Molecular Neuroscience

, Volume 61, Issue 2, pp 189–198 | Cite as

Update on Novel CCM Gene Mutations in Patients with Cerebral Cavernous Malformations

  • Concetta Scimone
  • Placido Bramanti
  • Concetta Alafaci
  • Francesca Granata
  • Francesco Piva
  • Carmela Rinaldi
  • Luigi Donato
  • Federica Greco
  • Antonina Sidoti
  • Rosalia D’Angelo
Article

Abstract

Cerebral cavernous malformations (CCMs) are lesions affecting brain microvessels. The pathogenesis is not clearly understood. Conventional classification criterion is based on genetics, and thus, familial and sporadic forms can be distinguished; however, classification of sporadic cases with multiple lesions still remains uncertain. To date, three CCM causative genes have been identified: CCM1/KRIT1, CCM2/MGC4607 and CCM3/PDCD10. In our previous mutation screening, performed in a cohort of 95 Italian patients, with both sporadic and familial cases, we identified several mutations in CCM genes. This study represents further molecular screening in a cohort of 19 Italian patients enrolled by us in the few last years and classified into familial, sporadic and sporadic with multiple lesions cases. Direct sequencing and multiplex ligation-dependent probe amplification (MLPA) analysis were performed to detect point mutations and large genomic rearrangements, respectively. Effects of detected mutations and single-nucleotide polymorphisms (SNPs) were evaluated by an in silico approach and by western blot analysis. A novel nonsense mutation in CCM1 and a novel missense mutation in CCM2 were detected; moreover, several CCM2 gene polymorphisms in sporadic CCM patients were reported. We believe that these data enrich the mutation spectrum of CCM genes, which is useful for genetic counselling to identify both familial and sporadic CCM cases, as early as possible.

Keywords

Brain vascular pathology CCM gene variants Early diagnosis Genetic test update Predictive medicine 

Notes

Compliance with Ethical Standards

DNA blood samples were obtained with written informed consent from all patients and normal controls. For underage patients, consent was obtained from the parents. Study protocol followed the guidelines of the local ethics committee, and the investigation was conducted with the ethical requirements defined in the Helsinki Declaration.

Conflict of Interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Concetta Scimone
    • 1
    • 2
  • Placido Bramanti
    • 3
  • Concetta Alafaci
    • 1
  • Francesca Granata
    • 1
  • Francesco Piva
    • 4
  • Carmela Rinaldi
    • 1
  • Luigi Donato
    • 1
    • 2
  • Federica Greco
    • 1
  • Antonina Sidoti
    • 1
    • 2
  • Rosalia D’Angelo
    • 1
  1. 1.Department of Biomedical and Dental Sciences and Morphofunctional Imaging, Division of Medical Biotechnologies and Preventive MedicineUniversity of MessinaMessinaItaly
  2. 2.Department of Cutting-Edge Medicine and Therapies, Biomolecular Strategies and Neuroscience, Section of Neuroscience-applied, Molecular Genetics and Predictive MedicineI.E.ME.S.TPalermoItaly
  3. 3.IRCCS Centro Neurolesi “Bonino-Pulejo”MessinaItaly
  4. 4.Department of Specialistic Clinical and Odontostomatological SciencesPolytechnic University of Marche RegionAnconaItaly

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