Sporadic Cerebral Cavernous Malformations: Report of Further Mutations of CCM Genes in 40 Italian Patients
Figure 1
Identification of two mutations in 3′UTR of the CCM1 gene in a sporadic CCM patient. (a) Left: partial wild-type sequence of 3′UTR of the CCM1 gene; right: mutated sequence of 3′UTR of the CCM1 gene showing the variants c.*132T>G and c.*137delC (arrows) in heterozygous condition. (b) Left: schematic representation of the sequence alignment of the hsa-miR-324-3p and hsa-miR-1913 with wild-type (WT) CCM1 mRNA (sequence target); right: schematic representation of the sequence alignment of hsa-miR-1281 with mutated CCM1 mRNA (sequence target). The “seed region” at the 5′ end of miRNA is shown in blue. While c.*132T>G is located 2 bp upstream of the predicted target sequence for has-miR-324-3p and hsa-miR-1913, the c.*137delC resides inside a sequence matching the seed of miRNAs. The c.*137 C deletion totally abolishes the interaction of hsa-miR-324-3p and hsa-miR-1913 with the sequence target. The two mutations together create a seed site in the 3′ UTR of mutated CCM1 mRNA for the interaction with hsa-miR-1281.
