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.
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Acknowledgements
L. Ortiz is recipient of fellowship from the red CIEN. This work was supported by grant PI041492 from the Fondo de Investigaciones Sanitarias, Ministerio de Sanidad y Consumo, 56/04 and 80/04 from Servicio Andaluz de Salud. We thank Michelle Sigrid Kremser for revising the English text.
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Received in revised form: 7 July 2006
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Ortiz, L., Costa, A.F., Bellido, M.L. et al. Study of cerebral cavernous malformation in Spain and Portugal. J Neurol 254, 322–326 (2007). https://doi.org/10.1007/s00415-006-0359-9
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DOI: https://doi.org/10.1007/s00415-006-0359-9