title: Mutation of the type X collagen gene (COL10A1) causes spondylometaphyseal dysplasia.
abstract: Spondylometaphyseal dysplasia (SMD) comprises a heterogeneous group of heritable skeletal dysplasias characterized by modifications of the vertebral bodies of the spine and metaphyses of the tubular bones. The genetic etiology of SMD is currently unknown; however, the type X collagen gene (COL10A1) is considered an excellent candidate, for two reasons: first, Schmid metaphyseal chondrodysplasia, a condition known to result from COL10A1 mutations, shows a significant phenotypic overlap with SMD; and, second, transgenic mice carrying deletions in type X collagen show SMD phenotypes. Hence, we examined the entire coding region of COL10A1 by direct sequencing of DNA from five unrelated patients with SMD and found a heterozygous missense mutation (Gly595Glu) cosegregating with the disease phenotype in one SMD family. This initial documented identification of a mutation in SMD expands our knowledge concerning the range of the pathological phenotypes that can be produced by aberrations of type X collagen (type X collagenopathy).
authors.affiliation: Laboratory of Genome Medicine, Institute of Medical Science, University of Tokyo, Japan. sikegawa@ims.u-tokyo.ac.jp
authors.forename: S
authors.initials: S
authors.lastname: Ikegawa
authors.forename: G
authors.initials: G
authors.lastname: Nishimura
authors.forename: T
authors.initials: T
authors.lastname: Nagai
authors.forename: T
authors.initials: T
authors.lastname: Hasegawa
authors.forename: H
authors.initials: H
authors.lastname: Ohashi
authors.forename: Y
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D002648:Child; D003094:Collagen / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D006579:Heterozygote; D006801:Humans; D007867:Leg Bones / Q000002:abnormalities; D008297:Male; D020125:Mutation, Missense; D016366:Open Reading Frames / Q000235:genetics; D010009:Osteochondrodysplasias / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA; D013131:Spine / Q000002:abnormalities
chemical_list: D003094:Collagen