Study of cerebral cavernous malformation in Spain and Portugal: high prevalence of a 14 bp deletion in exon 5 of MGC4607 (CCM2 gene).
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.
Ortiz
Lucía
L
Servicio de Biología Molecular, Hospital Universitario Virgen Macarena, Facultad de Medicina, Avda. Dr. Fedriani s/n, 41009, Sevilla, Spain.
Costa
Alzenira F
AF
Bellido
María L
ML
Solano
Francisca
F
García-Moreno
Jose M
JM
Gamero
Miguel A
MA
Izquierdo
Guillermo
G
Chadli
Amal
A
Falcao
Filipa
F
Ferro
Jose
J
Salas
Javier
J
Alvarez-Cermeño
Jose C
JC
Montori
Mariano
M
Ramos-Arroyo
María A
MA
Palomino
Alfredo
A
Pintado
Elizabeth
E
Lucas
Miguel
M
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
C502544:CCM2 protein, human; D002352:Carrier Proteins