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Detection of Novel Mutation in Ccm3 Causes Familial Cerebral Cavernous Malformations

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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.

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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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Authors and Affiliations

  1. Department of Biomedical Sciences and Morpho-functional Images, Division of Medical Biotechnologies and Preventive Medicine, University of Messina, Via C. Valeria 1, 98125, Messina, Italy

    Concetta Scimone, Alessia Ruggeri, Luigi Donato, Antonina Sidoti & Rosalia D’Angelo

  2. IRCCS Centro Neurolesi “Bonino-Pulejo”, Contrada Casazza, SS113, 98124, Messina, Italy

    Placido Bramanti

  3. Department of Neurology, Hippokration General Hospital, 49 Konstantinoupoleos Street, Thessaloniki, Greece

    Zoe Katsarou

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  1. Concetta Scimone
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  2. Placido Bramanti
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  3. Alessia Ruggeri
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  4. Zoe Katsarou
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  5. Luigi Donato
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  6. Antonina Sidoti
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  7. Rosalia D’Angelo
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Corresponding author

Correspondence to Antonina Sidoti.

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Scimone, C., Bramanti, P., Ruggeri, A. et al. Detection of Novel Mutation in Ccm3 Causes Familial Cerebral Cavernous Malformations. J Mol Neurosci 57, 400–403 (2015). https://doi.org/10.1007/s12031-015-0606-6

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  • DOI: https://doi.org/10.1007/s12031-015-0606-6

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