Mutation analysis of CCM1, CCM2 and CCM3 genes in a cohort of Italian patients with cerebral cavernous malformation

Rosalia D'Angelo, Valeria Marini, Carmela Rinaldi, Paola Origone, Alessandra Dorcaratto, Maria Avolio, Luca Goitre, Marco Forni, Valeria Capra, Concetta Alafaci, Cristina Mareni, Cecilia Garrè, Placido Bramanti, Antonina Sidoti, Saverio Francesco Retta, Aldo Amato

Research output: Contribution to journalArticlepeer-review


Cerebral cavernous malformations (CCMs) are vascular lesions of the CNS characterized by abnormally enlarged capillary cavities. CCMs can occur as sporadic or familial autosomal dominant form. Familial cases are associated with mutations in CCM1[K-Rev interaction trapped 1 (KRIT1)], CCM2 (MGC4607) and CCM3 (PDCD10) genes. In this study, a three-gene mutation screening was performed by direct exon sequencing, in a cohort of 95 Italian patients either sporadic or familial, as well as on their at-risk relatives. Sixteen mutations in 16 unrelated CCM patients were identified, nine mutations are novel: c.413T > C; c.601C > T; c.846 + 2T > G; c.1254delA; c.1255-4delGTA; c.1681-1682delTA in CCM1; c.48A > G; c.82-83insAG in CCM2; and c.396G > A in CCM3 genes. The samples, negative to direct exon sequencing, were investigated by MLPA to search for intragenic deletions or duplications. One deletion in CCM1 exon 18 was detected in a sporadic patient. Among familial cases 67% had a mutation in CCM1, 5.5% in CCM2, and 5.5% in CCM3, whereas in the remaining 22% no mutations were detected, suggesting the existence of either undetectable mutations or other CCM genes. This study represents the first extensive research program for a comprehensive molecular screening of the three known genes in an Italian cohort of CCM patients and their at-risk relatives.

Original languageEnglish
Pages (from-to)215-224
Number of pages10
JournalBrain Pathology
Issue number2
Publication statusPublished - Mar 2011


  • brain vascular pathologies
  • CCM genes
  • cerebral cavernous malformation
  • molecular genetic analysis in Italian patients

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pathology and Forensic Medicine
  • Clinical Neurology

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