BACKGROUND: Cerebral cavernous malformations are relatively rare vascular 
disorders that may affect any part of the central nervous system. This 
presentation has been associated with heterozygous mutations in CCM1/KRIT1, 
CCM2/malcavernin and CCM3/PDCD10. We aimed to investigate the genetic defect 
underlying multiple cerebral and vertebral cavernous malformations in a 
multigenerational Italian family.
CASE PRESENTATION: The proband is a 49-year-old man who underwent cerebral MRI 
in his thirties for persistent haeadache and tingling in his left arm and leg 
and was diagnosed with multiple supratentorial cavernous angiomas. A right 
frontal angioma with radiological evidence of a recent bleeding was surgically 
removed when he was 39 years old and he was thereafter asymptomatic. Magnetic 
resonance imaging revealed multiple cerebral cavernous malformations in seven 
members of his familily. Four subjects were asymptomatic. Other family mambers 
displayed heterogeneous clinical features including seizures and recurrent brain 
haemorrhages. Sequence analysis in the proband disclosed a novel heterozygous 
nucleotide substitution (c.263-10A > G) in intron 5 of CCM1. This variant is 
predicted to create an abnormal acceptor splice site and segregated in affected 
relatives available for molecular screening. The analysis of CCM1 transcript in 
proband's lymphocytes confirmed the partial retention of intron 3 resulting in a 
premature termination codon.
CONCLUSIONS: Our findings demonstrate that c.263-10A > G mutation is associated 
with cerebral cavernous malformations. A better knowledge of the 
disease-associated phenotype may lead to an early diagnosis and to an 
appropriate clinical surveillance in affected patients.