title: A novel MGP mutation in a consanguineous family: review of the clinical and molecular characteristics of Keutel syndrome.
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.
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hur
authors.forename: Gerald V
authors.initials: GV
authors.lastname: Raymond
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Kahler
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Riegert-Johnson
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Cohen
authors.forename: Simeon A
authors.initials: SA
authors.lastname: Boyadjiev
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D002114:Calcinosis / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002357:Cartilage Diseases / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D004423:Ear / Q000002:abnormalities; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005192:Family Health; D005260:Female; D006228:Hand Deformities, Congenital / Q000473:pathology; D006801:Humans; D008297:Male; D009154:Mutation; D011666:Pulmonary Valve Stenosis / Q000473:pathology; D013577:Syndrome; D000097568:Matrix Gla Protein
chemical_list: D002135:Calcium-Binding Proteins; D004247:DNA; D016326:Extracellular Matrix Proteins; D000097568:Matrix Gla Protein