Ehlers-Danlos syndrome type VIIA and VIIB result from splice-junction mutations or genomic deletions that involve exon 6 in the COL1A1 and COL1A2 genes of type I collagen

Peter H. Byers, Madeleine Duvic, Mary Atkinson, Meinhard Robinow, Lynne T. Smith, Stephen M. Krane, Marie T. Greally, Mark Ludman, Reuben Matalon, Susan Pauker, Deborah Quanbeck, Ulrike Schwarze

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Ehlers-Danlos syndrome (EDS) type VII results from defects in the conversion of type I procollagen to collagen as a consequence of mutations in the substrate that alter the protease cleavage site (EDS type VIIA and VIIB) or in the protease itself (EDS type VIIC). We identified seven additional families in which EDS type VII is either dominantly inherited (one family with EDS type VIIB) or due to new dominant mutations (one family with EDS type VIIA and five families with EDS type VIIB). In six families, the mutations alter the consensus splice junctions, and, in the seventh family, the exon is deleted entirely. The COL1A1 mutation produced the most severe phenotypic effects, whereas those in the COL1A2 gene, regardless of the location or effect, produced congenital hip dislocation and other joint instability that was sometimes very marked. Fractures are seen in some people with EDS type VII, consistent with alterations in mineral deposition on collagen fibrils in bony tissues. These new findings expand the array of mutations known to cause EDS type VII and provide insight into genotype/phenotype relationships in these genes.

Original languageEnglish (US)
Pages (from-to)94-105
Number of pages12
JournalAmerican Journal of Medical Genetics
Volume72
Issue number1
DOIs
StatePublished - Oct 3 1997

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Keywords

  • Alternative splicing
  • Collagen
  • Congenital hip dislocation
  • Ehlers-Danlos syndrome
  • Ehlers-Danlos syndrome type VII
  • Exon deletion
  • Exon skipping
  • Procollagen

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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