Especially the brain tumor has 57.1% deletion and 42.9% intron mutation,and the hepatocellular carcinoma also have 15.0% deletion and 26.7% intragenic mutation.
All above of these,Si-1 gene has higher deletion and intron mutation of brain tumor and hepatocellular carcinoma,showing this gene may be as a marker gene of brain tumor and hepatocellular carcinoma.
Especially the brain tumor has 57.1% deletion and 42.9% intron mutation,and the hepatocellular carcinoma also have 15.0% deletion and 26.7% intragenic mutation.
All of them have been characterized to represent DNA alterations by sequencing, including 8 point mutations (6 missence, 1 silent mutation and 1 in intron) and a 1 base pair insertion (introducing a stop codon downstream).
The activities of IVS2+21A→C heterozygotes and 94C→A/IVS2+21A→C compound heterozygotes were 60% and 10%, respectively, of the normal control mean, suggesting that the intron mutation affects enzyme activity.
The intron mutation activated numerous cryptic splice acceptor sites, generating normal and exon 13-deleted COL6A2 mRNA, and multiple aberrant transcripts containing frameshifts that were degraded through a nonsense-mediated decay mechanism.
Detection of such an intragenic mutation may be helpful not only in confirming diagnosis but also in elucidating functional domains of the SMN protein.