Missense mutations in hMLH1 and hMSH2 are associated with exonic splicing enhancers.

ABSTRACT: There is a critical need to understand why missense mutations are deleterious. The deleterious effects of missense mutations are commonly attributed to their impact on primary amino acid sequence and protein structure. However, several recent studies have shown that some missense mutations are deleterious because they disturb cis-acting splicing elements-so-called "exonic splicing enhancers" (ESEs). It is not clear whether the ESE-related deleterious effects of missense mutations are common. We have evaluated colocalization of pathogenic missense mutations (found in affected individuals) with high-score ESE motifs in the human mismatch-repair genes hMSH2 and hMLH1. We found that pathogenic missense mutations in the hMSH2 and hMLH1 genes are located in ESE sites significantly more frequentl

SUBMITTER: Gorlov IP 

PROVIDER: S-EPMC1180494 | biostudies-literature | 2003 Nov

REPOSITORIES: biostudies-literature