title: A radiographic, morphologic, biochemical and molecular analysis of a case of achondrogenesis type II resulting from substitution for a glycine residue (Gly691-->Arg) in the type II collagen trimer.
abstract: The type II collagenopathies form a continuous spectrum of clinical severity, ranging from lethal achondrogenesis type II and hypochondrogenesis, through spondyloepiphyseal dysplasia, spondyloepimetaphyseal dysplasia and Kniest dysplasia to the Stickler syndrome and familial precocious osteoarthropathy at the mildest end of the spectrum. We have carried out a radiographic, morphologic, biochemical and molecular study in a case of achondrogenesis type II. Electron micrographs showed inclusion bodies of dilated rough endoplasmic reticulum in the chondrocytes and the presence of sparse collagen fibers in the cartilage matrix. Protein analysis of collagen from cartilage indicated posttranslational overmodification of the major cyanogen bromide peptides, and suggested a mutation near the carboxyl terminus of the type II collagen molecule. Analysis at the DNA level demonstrated that the phenotype was produced by a single base change (G-->C) that resulted in the substitution of glycine691 by arginine in the type II collagen triple helical domain. We confirm previous observations in three cases of hypochondrogenesis that glycine substitutions in the alpha 1(II) chain can result in a phenotype at the most severe end of the type II collagenopathy spectrum.
authors.affiliation: Ahmanson Pediatric Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
authors.forename: G R
authors.initials: GR
authors.lastname: Mortier
authors.forename: D J
authors.initials: DJ
authors.lastname: Wilkin
authors.forename: W R
authors.initials: WR
authors.lastname: Wilcox
authors.forename: D L
authors.initials: DL
authors.lastname: Rimoin
authors.forename: R S
authors.initials: RS
authors.lastname: Lachman
authors.forename: D R
authors.initials: DR
authors.lastname: Eyre
authors.forename: D H
authors.initials: DH
authors.lastname: Cohn
mesh_terms: D000028:Abortion, Induced; D000130:Achondroplasia / Q000151:congenital / Q000000981:diagnostic imaging* / Q000235:genetics*; D001483:Base Sequence; D002356:Cartilage / Q000002:abnormalities / Q000737:chemistry; D003094:Collagen / Q000737:chemistry / Q000235:genetics*; D003095:Collagen Diseases / Q000150:complications / Q000196:embryology / Q000235:genetics*; D003488:Cyanogen Bromide / Q000737:chemistry; D004247:DNA / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008853:Microscopy; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010455:Peptides / Q000032:analysis / Q000737:chemistry; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011247:Pregnancy; D011859:Radiography; D012967:Sodium Dodecyl Sulfate
chemical_list: D010455:Peptides; D012967:Sodium Dodecyl Sulfate; D003094:Collagen; D004247:DNA; D003488:Cyanogen Bromide