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Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the initial rate-limiting step in mitochondrial fatty acid beta-oxidation. VLCAD deficiency is clinically heterogenous, with three major phenotypes: a severe childhood form, with early onset, high mortality, and high incidence of cardiomyopathy; a milder childhood form, with later onset, usually with(More)
Acyl-CoA dehydrogenase (ACAD) defects in isoleucine and valine catabolism have been proposed in clinically diverse patients with an abnormal pattern of metabolites in their urine, but they have not been proved enzymatically or genetically, and it is unknown whether one or two ACADs are involved. We investigated a patient with isolated(More)
The idea that point mutations in exons may affect splicing is intriguing and adds an additional layer of complexity when evaluating their possible effects. Even in the best-studied examples, the molecular mechanisms are not fully understood. Here, we use patient cells, model minigenes, and in vitro assays to show that a missense mutation in exon 5 of the(More)
Deep intronic mutations are often ignored as possible causes of human diseases. A deep intronic mutation in the MTRR gene, c.903+469T>C, is the most frequent mutation causing the cblE type of homocystinuria. It is well known to be associated with pre-mRNA mis-splicing, resulting in pseudoexon inclusion; however, the pathological mechanism remains unknown.(More)
Spinal Muscular Atrophy is caused by homozygous loss of SMN1 with phenotypic modulation by SMN2. SMN2 expresses only limited amounts of full-length transcript due to skipping of exon 7 caused by disruption of an SF2/ASF binding ESE. Additionally, hnRNP A1 has been reported to inhibit inclusion of SMN2 exon 7. We previously reported high similarity between(More)
Mutations that cause accumulation or rapid degradation owing to protein misfolding are a frequent cause of inherited disease in humans. In Escherichia coli, Clpp protease is one of the components of the protein quality control system that handles misfolded proteins. In the present study, we have characterized the mouse Clpp cDNA sequence, the organization(More)
Deep intronic mutations are often ignored as possible causes of human diseases. A deep intronic mutation in the MTRR gene, c.9031469T4C, is the most frequent mutation causing the cblE type of homocystinuria. It is well known to be associated with pre-mRNA missplicing, resulting in pseudoexon inclusion ; however, the pathological mechanism remains unknown.(More)
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