Journal Article

A Splice-Junction Mutation in the Region of <i>COL5A1</i> that Codes for the Carboxyl Propeptide of Proα1(V) Chains Results in the <i>Gravis</i> Form of the Ehlers-Danlos Syndrome (Type I)

Richard J. Wenstrup, Gregory T. Langland, Marcia C. Willing, Vinita N. D'Souza and William G. Cole

in Human Molecular Genetics

Volume 5, issue 11, pages 1733-1736
Published in print November 1996 | ISSN: 0964-6906
e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/5.11.1733
A Splice-Junction Mutation in the Region of COL5A1 that Codes for the Carboxyl Propeptide of Proα1(V) Chains Results in the Gravis Form of the Ehlers-Danlos Syndrome (Type I)

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Type V collagen is a constituent of type I collagen-rich fibrils in many connective tissues and is a regulator of fibril diameter. In tissues, type V collagen is a heterotrimer with the molecular structure: α1(V)2α2(V) or α1(V)α2(V)α3(V). We report that genomic polymorphisms at the proα1(V) gene (COL5A1) locus cosegregated with the gravis form of Ehlers-Danlos syndrome (EDS) (type I) in a three generation family. Affected family members, who had classical features including joint hyperextensibility, fragile skin, and widened, atrophic scars, were heterozygous for a 4 bp deletion at positions from +3 to +6 of intron 65, which resulted in removal of exon 65 sequences from processed mRNAs. Since exon 65 encodes 78 residues of the carboxyl propeptide, the expected result of this mutation is reduced efficiency in incorporating mutant proα1(V) chains into type V collagen molecules and reduced type V collagen synthesis. These studies indicate that heterozygous mutations in COL5A1 can result in EDS type I. However, linkage studies in other EDS I families indicate the disorder is heterogeneous; linkage to both COL5A1 and COL5A2 was excluded in two other families with EDS I while a fourth family was concordant for linkage to COL5A1 (Z = 2.11; θ = 0.00).

Journal Article.  3677 words.  Illustrated.

Subjects: Genetics and Genomics

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