Skip to main content
Journal cover image

Allelic and locus heterogeneity in inherited venous malformations.

Publication ,  Journal Article
Calvert, JT; Riney, TJ; Kontos, CD; Cha, EH; Prieto, VG; Shea, CR; Berg, JN; Nevin, NC; Simpson, SA; Pasyk, KA; Speer, MC; Peters, KG; Marchuk, DA
Published in: Hum Mol Genet
July 1999

Venous malformations are low-flow vascular lesions consisting of disorganized thin-walled vascular channels. These can occur sporadically but also as an autosomal dominant condition termed venous malformations, cutaneous and mucosal (VMCM; OMIM 600195). In two large unrelated kindreds mapping to chromosome 9, the identical R849W missense mutation was identified in the first kinase domain of Tie2, an endothelial cell-specific receptor tyrosine kinase. We report here the identification of four new kindreds with inherited venous malformations. Unlike the initial two families described, these four families demonstrate allelic and locus heterogeneity. In one of these families, the R849W mutation co-segregates with the disease phenotype. Three other families with venous malformations lack this mutation. One of these families is linked to markers near TIE2 on chromosome 9. In this family, we identified a novel mutation within the first kinase domain of Tie2 resulting in a Y897S change. Results from COS-1 cell transfections using expression constructs containing either the R849W or the Y897S mutation suggest that the receptors containing either mutation show ligand-independent hyperphosphorylation. These results suggest a gain-of-function mechanism for development of venous malformations in these families. Of the two remaining families, one excludes linkage to the TIE2 locus, establishing the existence of at least one additional locus for dominantly inherited venous malformations.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Hum Mol Genet

DOI

ISSN

0964-6906

Publication Date

July 1999

Volume

8

Issue

7

Start / End Page

1279 / 1289

Location

England

Related Subject Headings

  • Vascular Diseases
  • Transfection
  • Sequence Alignment
  • Phosphorylation
  • Pedigree
  • Mutation
  • Molecular Sequence Data
  • Male
  • Ligands
  • Humans
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Calvert, J. T., Riney, T. J., Kontos, C. D., Cha, E. H., Prieto, V. G., Shea, C. R., … Marchuk, D. A. (1999). Allelic and locus heterogeneity in inherited venous malformations. Hum Mol Genet, 8(7), 1279–1289. https://doi.org/10.1093/hmg/8.7.1279
Calvert, J. T., T. J. Riney, C. D. Kontos, E. H. Cha, V. G. Prieto, C. R. Shea, J. N. Berg, et al. “Allelic and locus heterogeneity in inherited venous malformations.Hum Mol Genet 8, no. 7 (July 1999): 1279–89. https://doi.org/10.1093/hmg/8.7.1279.
Calvert JT, Riney TJ, Kontos CD, Cha EH, Prieto VG, Shea CR, et al. Allelic and locus heterogeneity in inherited venous malformations. Hum Mol Genet. 1999 Jul;8(7):1279–89.
Calvert, J. T., et al. “Allelic and locus heterogeneity in inherited venous malformations.Hum Mol Genet, vol. 8, no. 7, July 1999, pp. 1279–89. Pubmed, doi:10.1093/hmg/8.7.1279.
Calvert JT, Riney TJ, Kontos CD, Cha EH, Prieto VG, Shea CR, Berg JN, Nevin NC, Simpson SA, Pasyk KA, Speer MC, Peters KG, Marchuk DA. Allelic and locus heterogeneity in inherited venous malformations. Hum Mol Genet. 1999 Jul;8(7):1279–1289.
Journal cover image

Published In

Hum Mol Genet

DOI

ISSN

0964-6906

Publication Date

July 1999

Volume

8

Issue

7

Start / End Page

1279 / 1289

Location

England

Related Subject Headings

  • Vascular Diseases
  • Transfection
  • Sequence Alignment
  • Phosphorylation
  • Pedigree
  • Mutation
  • Molecular Sequence Data
  • Male
  • Ligands
  • Humans