A novel MGP mutation in a consanguineous family

Review of the clinical and molecular characteristics of Keutel syndrome

David J. Hur, Gerald V. Raymond, Stephen G. Kahler, Douglas L. Riegert-Johnson, Bernard A Cohen, Simeon A. Boyadjiev

Research output: Contribution to journalArticle

Abstract

Keutel syndrome (KS) [OMIM 245150] is a rare autosomal recessive condition, characterized by abnormal cartilage calcification. Mutations in the matrix Gla protein gene (MGP) have been previously reported in three unrelated KS families. MGP is an extracellular matrix protein that acts as a calcification inhibitor by repressing bone morphogenetic protein 2 (BMP2). Loss-of-function mutations of MGP result in abnormal calcification of the soft tissues, a cardinal feature of KS. We report the fourth MGP mutation (IVS2 + 1G > A) in a consanguineous Arab family, which results in the loss of the consensus donor splice site at the exon 2-intron 2 junction. In addition to the typical manifestations, we observed abnormalities in the white matter of the brain, optic nerve atrophy, and mid-dermal elastolysis in the affected individuals of this family. This report broadens the clinical phenotype observed in patients with KS. The effect of the IVS2 + 1G > A mutation is consistent with the previously reported loss-of-function mutations of MGP.

Original languageEnglish (US)
Pages (from-to)36-40
Number of pages5
JournalAmerican Journal of Medical Genetics
Volume135 A
Issue number1
DOIs
StatePublished - May 15 2005

Fingerprint

Mutation
Genes
Genetic Databases
Optic Atrophy
Bone Morphogenetic Protein 2
RNA Splice Sites
Extracellular Matrix Proteins
Optic Nerve
Introns
Cartilage
Exons
Keutel syndrome
matrix Gla protein
Phenotype
Skin
Brain

Keywords

  • Keutel syndrome
  • MGP gene
  • Mid-dermal elastolysis

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

A novel MGP mutation in a consanguineous family : Review of the clinical and molecular characteristics of Keutel syndrome. / Hur, David J.; Raymond, Gerald V.; Kahler, Stephen G.; Riegert-Johnson, Douglas L.; Cohen, Bernard A; Boyadjiev, Simeon A.

In: American Journal of Medical Genetics, Vol. 135 A, No. 1, 15.05.2005, p. 36-40.

Research output: Contribution to journalArticle

Hur, David J. ; Raymond, Gerald V. ; Kahler, Stephen G. ; Riegert-Johnson, Douglas L. ; Cohen, Bernard A ; Boyadjiev, Simeon A. / A novel MGP mutation in a consanguineous family : Review of the clinical and molecular characteristics of Keutel syndrome. In: American Journal of Medical Genetics. 2005 ; Vol. 135 A, No. 1. pp. 36-40.
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