Cerebral cavernous malformations (CCM) are vascular malformations, mostly 
located in the central nervous system, which occur in 0.1-0.5% of the 
population. They are characterized by abnormally enlarged and often leaking 
capillary cavities without intervening neural parenchyma. Some are clinically 
silent, whereas others cause seizures, intracerebral haemorrhage or focal 
neurological deficits. These vascular malformations can arise sporadically or 
may be inherited as an autosomal dominant condition with incomplete penetrance. 
At least 45% of families affected with cerebral cavernous malformations harbour 
a mutation in Krev interaction trapped-1 (Krit1) gene (cerebral cavernous 
malformation gene-1, CCM1). This gene contains 16 coding exons which encode a 
736-amino acid protein containing three ankyrin repeats and a FERM domain. 
Neither the CCM1 pathogenetic mechanisms nor the function of the Krit1 protein 
are understood so far, although several hypotheses have been inferred from the 
predicted consequences of Krit1 mutations as well as from the identification of 
Krit1 as a binding partner of Rap1A, ICAP1A and microtubules. Here, we report 
the identification of Krit1B, a novel Krit1 isoform characterized by the 
alternative splicing of the 15th coding exon. We show that the Krit1B splice 
isoform is widely expressed in mouse cell lines and tissues, whereas its 
expression is highly restricted in human. In addition, we developed a real-time 
PCR strategy to accurately quantify the relative ratio of the two Krit1 
alternative transcripts in different tissues, demonstrating a Krit1B/Krit1A 
ratio up to 20% in mouse thymus, but significantly lower ratios in other 
tissues. Bioinformatic analysis using exon/gene-prediction, comparative 
alignment and structure analysis programs supported the existence of Krit1 
alternative transcripts lacking the 15th coding exon and showed that the 
splicing out of this exon occurs outside of potentially important Krit1 
structural domains but in a region required for association with Rap1A, 
suggesting a subtle, yet important effect on the protein function. Our results 
indicate that maintenance of a proper ratio between Krit1A and Krit1B could be 
functionally relevant and suggest that the novel Krit1B isoform might expand our 
understanding of the role of Krit1 in CCM1 pathogenesis.