Exon skipping in IVD RNA processing in isovaleric acidemia caused by point mutations in the coding region of the IVD gene.

ABSTRACT: Isovaleric acidemia (IVA) is a recessive disorder caused by a deficiency of isovaleryl-CoA dehydrogenase (IVD). We have reported elsewhere nine point mutations in the IVD gene in fibroblasts of patients with IVA, which lead to abnormalities in IVD protein processing and activity. In this report, we describe eight IVD gene mutations identified in seven IVA patients that result in abnormal splicing of IVD RNA. Four mutations in the coding region lead to aberrantly spliced mRNA species in patient fibroblasts. Three of these are amino acid altering point mutations, whereas one is a single-base insertion that leads to a shift in the reading frame of the mRNA. Two of the coding mutations strengthen pre-existing cryptic splice acceptors adjacent to the natural splice junctions and apparently inte

SUBMITTER: Vockley J 

PROVIDER: S-EPMC1288088 | biostudies-literature | 2000 Feb

REPOSITORIES: biostudies-literature