KRIT1 and cerebral cavernous malformation: Although we found that both CCM1 and CCM3 are less polymorphic regarding alternative splicing events in our hands, an alternative spliced CCM1 isoform lacking the 15th coding exon, Krit1B, has been reported to be expressed at relatively high levels in mouse tissues and cell lines, but much less expression detected in humans40; interestingly, an “in-frame deletion” found in a large CCM cohort mutation screening, which results in the lack of entire exon 18 of CCM1 gene, was found to have dramatically decreased expression level as well41.