TY - JOUR
T1 - A novel MGP mutation in a consanguineous family
T2 - Review of the clinical and molecular characteristics of Keutel syndrome
AU - Hur, David J.
AU - Raymond, Gerald V.
AU - Kahler, Stephen G.
AU - Riegert-Johnson, Douglas L.
AU - Cohen, Bernard A.
AU - Boyadjiev, Simeon A.
PY - 2005/5/15
Y1 - 2005/5/15
N2 - 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.
AB - 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.
KW - Keutel syndrome
KW - MGP gene
KW - Mid-dermal elastolysis
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U2 - 10.1002/ajmg.a.30680
DO - 10.1002/ajmg.a.30680
M3 - Review article
C2 - 15810001
AN - SCOPUS:18244394309
SN - 1552-4825
VL - 135 A
SP - 36
EP - 40
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 1
ER -