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Journal of Molecular Neuroscience

, Volume 57, Issue 3, pp 400–403 | Cite as

Detection of Novel Mutation in Ccm3 Causes Familial Cerebral Cavernous Malformations

  • Concetta Scimone
  • Placido Bramanti
  • Alessia Ruggeri
  • Zoe Katsarou
  • Luigi Donato
  • Antonina SidotiEmail author
  • Rosalia D’Angelo
Article

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

Familial cerebral cavernous malformations CCM3 mutation Incomplete penetrance Impaired angiogenesis 

Notes

Acknowledgments

We are thankful to Dr. Eugenia Avdellidou and Dr. Eleni Fourkala of the Department of Neurology, Hippokration General Hospital, Thessaloniki, Greece, for their contribution to this study.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Concetta Scimone
    • 1
  • Placido Bramanti
    • 2
  • Alessia Ruggeri
    • 1
  • Zoe Katsarou
    • 3
  • Luigi Donato
    • 1
  • Antonina Sidoti
    • 1
    Email author
  • Rosalia D’Angelo
    • 1
  1. 1.Department of Biomedical Sciences and Morpho-functional Images, Division of Medical Biotechnologies and Preventive MedicineUniversity of MessinaMessinaItaly
  2. 2.IRCCS Centro Neurolesi “Bonino-Pulejo”MessinaItaly
  3. 3.Department of NeurologyHippokration General HospitalThessalonikiGreece

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