Splicing analysis of unclassified variants in COL2A1 and COL11A1 identifies deep intronic pathogenic mutations.

ABSTRACT: UK NHS diagnostic service sequence analysis of genes generally examines and reports on variations within a designated region 5' and 3' of each exon, typically 30 bp up and downstream. However, because of the degenerate nature of the splice sites, intronic variants outside the AG and GT dinucleotides of the acceptor and donor splice sites (ASS and DSS) are most often classified as being of unknown clinical significance, unless there is some functional evidence of their pathogenicity. It is now becoming clear that mutations deep within introns can also interfere with normal processing of pre-mRNA and result in pathogenic effects on the mature transcript. In diagnostic laboratories, these deep intronic variants most often fall outside of the regions analysed and so are rarely reported. With t

SUBMITTER: Richards AJ 

PROVIDER: S-EPMC3330208 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature