Transcriptional and translational effects of intronic CAPN3 gene mutations.
Bottom Line: The absence or severe reduction of protein demonstrated their deleterious effect at translational level.We concluded that bioinformatic tools are valuable to suggest the potential effects of intronic variants; however, the experimental demonstration of the pathogenicity is not always easy to do even when using RNA analysis (low abundance, degradation mechanisms), and it might not be successful unless splicing-specific-PCR tests are used.A comprehensive approach is therefore recommended to identify and describe unclassified variants in order to offer essential data for basic and clinical geneticists.
Affiliation: Department of Neurosciences, University of Padova, Italy.Show MeSH
Related in: MedlinePlus
Mentions: This mutation was identified in 6 unrelated LGMD2A patients in our series, all from the same administrative district of the Veneto Region (a possible founder effect followed by genetic isolation might have occurred). Among the 6 patients with this mutation, one was the object of a family study (Figure 3): we conducted both a segregation analysis of the mutant allele and a study of the effect of this mutation at calpain-3 protein level in 2 different family members (a muscle biopsy was obtained from both an affected girl and her heterozygote father, who reported hyperCKemia before the diagnosis was obtained in his daughter).
Affiliation: Department of Neurosciences, University of Padova, Italy.