title: A human chondrodysplasia due to a mutation in a TGF-beta superfamily member.
abstract: The TGF-beta superfamily comprises a number of functionally diverse growth factors/signalling molecules (1) which elicit their response upon binding to serine-threonine kinase receptors (2). We recently reported the isolation and characterization of two new members of the family, designated cartilage-derived morphogenetic protein (CDMP) 1 and 2 (ref. 3) which are closely related to the sub-family of bone morphogenetic proteins. CDMP-1 is predominantly expressed at sites of skeletal morphogenesis (3), and we now show that a mutation in hCDMP-1 is associated with a recessive human chondrodysplasia (acromesomelic chondrodysplasia, Hunter-Thompson type (4,5)). The disorder, characterized by skeletal abnormalities restricted to the limbs andlimb joints, is phenotypically similar to murine brachypodism (bp) which is due to mutations in growth/differentiation factor-5 (Gdf-5) (6), the mouse homologue of hCDMP-1. Affected individuals are homozygous for a 22-bp (tandem-duplication) frameshift mutation in the mature region of CDMP-1. The resulting phenotype provides direct evidence for the involvement of CDMP-1 in human skeletal development and represents the first human disorder attributable to a mutation in a TGF-beta superfamily member.
authors.affiliation: Bone Research Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: J T
authors.initials: JT
authors.lastname: Thomas
authors.forename: K
authors.initials: K
authors.lastname: Lin
authors.forename: M
authors.initials: M
authors.lastname: Nandedkar
authors.forename: M
authors.initials: M
authors.lastname: Camargo
authors.forename: J
authors.initials: J
authors.lastname: Cervenka
authors.forename: F P
authors.initials: FP
authors.lastname: Luyten
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D019485:Bone Morphogenetic Proteins; D004247:DNA; D005260:Female; D016368:Frameshift Mutation; D055428:Growth Differentiation Factor 5; D006133:Growth Substances / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010009:Osteochondrodysplasias / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D019485:Bone Morphogenetic Proteins; D055428:Growth Differentiation Factor 5; D006133:Growth Substances; D016212:Transforming Growth Factor beta; D004247:DNA