Introduction: Cerebral cavernous malformation (CCM) is a vascular disorder characterized by the presence of central nervous system cavernomas. In familial forms, mutations in three genes (CCM1/KRIT1, CCM2/MGC4607 and CCM3/PDCD10) were identified. We describe a Portuguese family harboring a novel CCM1 mutation.
Case presentation: The proband is a woman who at the age of 55 years started to have complex partial seizures and episodic headache. Although nothing was found during her neurological examination, brain MRI showed bilateral, supra- and infratentorial cavernomas. She had a sister who, at the age 61 years, suffered a tonic-clonic seizure. Neurological examination was normal and imaging investigation demonstrated a right frontal intracerebral hemorrhage and multiple cavernomas. In the following years, she suffered several complex partial seizures and had a new intracerebral hemorrhage located in the right temporal lobe. Genetic analysis was performed and a novel nucleotide substitution, i.e. c.1927C>T (p.Gln643*) within the exon 17 of the CCM1 gene, was detected in both sisters. The substitution encodes a stop codon, with a consequent truncated KRIT1 protein, therefore supporting its pathogenic role. Further affected family members were detected, suggesting an autosomal dominant pattern of inheritance.
Conclusion: We report a Portuguese family with a novel CCM1 (KRIT1) mutation - c.1927C>T (p.Gln643*). A better knowledge of the phenotype-genotype correlation is needed to improve the management of CCM patients.
Keywords: CCM1 mutation; Cavernoma; Cerebral cavernous malformation; KRIT1.