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A novel MGP mutation in a consanguineous family: Review of the clinical and molecular characteristics of Keutel syndrome
Author(s) -
Hur David J.,
Raymond Gerald V.,
Kahler Stephen G.,
RiegertJohnson Douglas L.,
Cohen Bernard A.,
Boyadjiev Simeon A.
Publication year - 2005
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.30680
Subject(s) - genetics , mutation , consanguinity , medicine , biology , computational biology , gene
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 . © 2005 Wiley‐Liss, Inc.