Hereditary cancer genes are highly susceptible to splicing mutations

• DOI: 10.1371/journal.pgen.1007231
• Publication Date: 2018-03-05T13:24:36Z
• Authors: Christy L. Rhine; Kamil J. Cygan; Rachel Soemedi; Samantha Maguire; Michael F. Murray; Sean F. Monaghan; William G. Fairbr...
• Keywords: Minigene; Exonic splicing enhancer; MSH2; Lynch Syndrome; MLH1; Exon skipping

Substitutions that disrupt pre-mRNA splicing are a common cause of genetic disease. On average, 13.4% all hereditary disease alleles classified as mutations mapping to the canonical 5' and 3' splice sites. However, present in exons deeper intronic positions vastly underreported. A recent re-analysis coding exon 10 Lynch Syndrome gene, MLH1, revealed an extremely high rate (77%) lead defective splicing. This finding is confirmed by extending sampling five other MLH1 gene. Further analysis suggests more general phenomenon driving Syndrome. Of 36 tested, 11 disrupted Furthermore, analyzing past reports suggest sites also occupy much higher fraction (36%) total than expected. When performing comprehensive human genes, we found three main causal genes Syndrome, MSH2, PMS2, belonged class 86 which enriched for mutations. Other cancer were susceptible genes. The enrichment cancers strongly argues additional priority interpreting clinical sequencing data relation