Study of cerebral cavernous malformation in Spain and Portugal: high prevalence of a 14 bp deletion in exon 5 of MGC4607 (CCM2 gene)

J Neurol. 2007 Mar;254(3):322-6. doi: 10.1007/s00415-006-0359-9. Epub 2007 Mar 7.


Objective: We aimed to study clinical, radiological and molecular genetic features of patients with cerebral cavernous malformations (CCMs) from the Iberian Peninsula.

Methods: We screened Krit1(CCM1), MGC4607(CCM2), and PDCD10(CCM3) by systematic SSCP and direct sequencing of coding exons in 48 nuclear families and 30 sporadic cases of CCM from Spain and Portugal.

Results: Screening of CCM patients detected nine different mutations in 19 families. We found four new mutations in Krit1. Three of them were caused by either a small insertion or deletion, which lead to frameshift and premature termination codons. We also found a missense L308H mutation located in a highly conserved sequence within the ankyrin domain of Krit1. In CCM2, we found a redundant 14 bp deletion in exon 5 of MGC4607 which predicts a truncated protein at residue 230. We did not find mutations in CCM3.

Conclusions: Finding that the 14 bp deletion was present in eleven families from the Iberian Peninsula indicates a high prevalence of this mutation. This redundant CCM2 mutation is worth considering in molecular diagnosis and genetic counselling of cerebral cavernous malformations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / genetics*
  • Central Nervous System Neoplasms / genetics*
  • DNA Mutational Analysis / methods
  • Exons*
  • Family Health*
  • Hemangioma, Cavernous, Central Nervous System / genetics*
  • Humans
  • Portugal / epidemiology
  • Sequence Deletion*
  • Spain / epidemiology


  • CCM2 protein, human
  • Carrier Proteins