leupeptins and Marfan-Syndrome

leupeptins has been researched along with Marfan-Syndrome* in 1 studies

Other Studies

1 other study(ies) available for leupeptins and Marfan-Syndrome

ArticleYear
Novel exon nucleotide substitution at the splice junction causes a neonatal Marfan syndrome.
    Clinical genetics, 2010, Volume: 77, Issue:5

    The fibrillin-1 gene (FBN1) mutations are associated with a broad spectrum of disorders including Marfan syndrome (MFS) and show great clinical heterogeneity. An underrepresentation for mutations leading to premature termination codon (PTC) in FBN1 exons 24-32 was found in neonatal or severe MFS but the underlying cause was unclear. This study thoroughly examined two FBN1 mutations on exons 24-32 region to illustrate the molecular mechanisms underlying these FBN1 mutations on MFS etiology. Two nucleotide substitutions, c.3208G> C, the last nucleotide of exon 26, and c.3209A>G, the first nucleotide of exon 27, affecting the same amino acid, p.D1070H and p.D1070G, respectively, gave very different phenotypes. We demonstrate that c.3208G>C generates two alternatively spliced transcripts, while c.3209A>G does not affect the splicing. We further demonstrate that the aberrantly spliced transcripts do not go through nonsense-mediated decay, but rather produce unstable, premature protein peptides that are degraded by endoplasmic reticulum associated degradation. The molecular mechanism outlined here defines a model for the pathogenesis of PTC-containing mutation within the exons 24-32 of FBN1 in MFS. Furthermore, our data suggest that PTC mutation within this region may lead to early lethality in neonatal MFS.

    Topics: Base Sequence; Blotting, Western; Cell Line; Codon, Nonsense; Endoplasmic Reticulum; Exons; Fatal Outcome; Female; Fibrillin-1; Fibrillins; Humans; Infant, Newborn; Intracellular Space; Leupeptins; Marfan Syndrome; Microfilament Proteins; Microscopy, Fluorescence; Molecular Sequence Data; Mutant Proteins; Mutation; Nucleotides; Pregnancy; Protein Processing, Post-Translational; RNA Splice Sites; RNA Splicing; RNA Stability

2010