title: Study of cerebral cavernous malformation in Spain and Portugal: high prevalence of a 14 bp deletion in exon 5 of MGC4607 (CCM2 gene).
abstract: 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.
authors.affiliation: Servicio de Biología Molecular, Hospital Universitario Virgen Macarena, Facultad de Medicina, Avda. Dr. Fedriani s/n, 41009, Sevilla, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: Ortiz
authors.forename: Alzenira F
authors.initials: AF
authors.lastname: Costa
authors.forename: María L
authors.initials: ML
authors.lastname: Bellido
authors.forename: Francisca
authors.initials: F
authors.lastname: Solano
authors.forename: Jose M
authors.initials: JM
authors.lastname: García-Moreno
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Gamero
authors.forename: Guillermo
authors.initials: G
authors.lastname: Izquierdo
authors.forename: Amal
authors.initials: A
authors.lastname: Chadli
authors.forename: Filipa
authors.initials: F
authors.lastname: Falcao
authors.forename: Jose
authors.initials: J
authors.lastname: Ferro
authors.forename: Javier
authors.initials: J
authors.lastname: Salas
authors.forename: Jose C
authors.initials: JC
authors.lastname: Alvarez-Cermeño
authors.forename: Mariano
authors.initials: M
authors.lastname: Montori
authors.forename: María A
authors.initials: MA
authors.lastname: Ramos-Arroyo
authors.forename: Alfredo
authors.initials: A
authors.lastname: Palomino
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pintado
authors.forename: Miguel
authors.initials: M
authors.lastname: Lucas
mesh_terms: D002352:Carrier Proteins / Q000235:genetics*; D016543:Central Nervous System Neoplasms / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005091:Exons; D005192:Family Health; D020786:Hemangioma, Cavernous, Central Nervous System / Q000235:genetics*; D006801:Humans; D011174:Portugal / Q000453:epidemiology; D017384:Sequence Deletion; D013030:Spain / Q000453:epidemiology
chemical_list: C502544:CCM2 protein, human; D002352:Carrier Proteins