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A functional mutation in the terminal exon of elastin in severe, early-onset chronic obstructive pulmonary disease.

ABSTRACT: We describe a novel variant in the terminal exon of human elastin, c.2318 G > A, resulting in an amino acid substitution of glycine 773 to aspartate (G773D) in a pedigree with severe early-onset chronic obstructive pulmonary disease (COPD). Transfection studies with elastin cDNAs demonstrate that the glycine to aspartate change compromises the ability of the mutant protein to undergo normal elastin assembly. Other functional consequences of this amino acid substitution include altered proteolytic susceptibility of the C-terminal region of elastin and reduced interaction of the exon 36 sequence with matrix receptors on cells. These results suggest that the G773D variant confers structural and functional consequences relevant to the pathogenesis of COPD.

SUBMITTER: Kelleher CM

PROVIDER: S-EPMC2715343 | biostudies-literature | 2005 Oct

REPOSITORIES: biostudies-literature

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A functional mutation in the terminal exon of elastin in severe, early-onset chronic obstructive pulmonary disease.

Kelleher Cassandra M CM Silverman Edwin K EK Broekelmann Thomas T Litonjua Augusto A AA Hernandez Melvin M Sylvia Jody S JS Stoler Joan J Reilly John J JJ Chapman Harold A HA Speizer Frank E FE Weiss Scott T ST Mecham Robert P RP Raby Benjamin A BA

American journal of respiratory cell and molecular biology 20050804 4

We describe a novel variant in the terminal exon of human elastin, c.2318 G > A, resulting in an amino acid substitution of glycine 773 to aspartate (G773D) in a pedigree with severe early-onset chronic obstructive pulmonary disease (COPD). Transfection studies with elastin cDNAs demonstrate that the glycine to aspartate change compromises the ability of the mutant protein to undergo normal elastin assembly. Other functional consequences of this amino acid substitution include altered proteolyti ...[more]

PMID: 16081882

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Dataset Information

A functional mutation in the terminal exon of elastin in severe, early-onset chronic obstructive pulmonary disease.

Publications

A functional mutation in the terminal exon of elastin in severe, early-onset chronic obstructive pulmonary disease.

Similar Datasets

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