title: Heterozygous C-propeptide mutations in COL1A1: osteogenesis imperfecta type IIC and dense bone variant.
abstract: Osteogenesis imperfecta type IIC (OI IIC) is a rare variant of lethal OI that has been considered to be an autosomal recessive trait. Twisted, slender long bones with dense metaphyseal margins and normal vertebral bodies in OI IIC contrast with crumpled, thick long bones and multiple vertebral compression fractures in OI IIA. Here, we report on two sporadic patients with classical OI IIC and a pair of siblings, with features of OI IIC but less distortion of the tubular bones (OI dense bone variant). One case with OI IIC and the sibs had novel heterozygous mutations in the C-propeptide region of COL1A1, while the second patient with clear-cut OI IIC had no mutation in this region. Histological examination in the two sporadic cases showed a network of broad, interconnected cartilaginous trabeculae with thin osseous seams in the metaphyses. These changes differed from the narrow and short metaphyseal trabeculae found in other lethal or severe cases of OI. Our experience sheds light on the genetics and etiology of OI IIC and on its phenotypic spectrum.
authors.affiliation: Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Takagi
authors.forename: Naoaki
authors.initials: N
authors.lastname: Hori
authors.forename: Yasutsugu
authors.initials: Y
authors.lastname: Chinen
authors.forename: Kenji
authors.initials: K
authors.lastname: Kurosawa
authors.forename: Yukichi
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Kikuko
authors.initials: K
authors.lastname: Oku
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sakata
authors.forename: Ryuji
authors.initials: R
authors.lastname: Fukuzawa
authors.forename: Gen
authors.initials: G
authors.lastname: Nishimura
authors.forename: Jürgen
authors.initials: J
authors.lastname: Spranger
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Hasegawa
mesh_terms: D001483:Base Sequence; D015519:Bone Density / Q000235:genetics; D001842:Bone and Bones / Q000002:abnormalities / Q000473:pathology; D002648:Child; D024042:Collagen Type I / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D005260:Female; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D008297:Male; D009154:Mutation; D010013:Osteogenesis Imperfecta / Q000235:genetics* / Q000473:pathology*; D010641:Phenotype; D011498:Protein Precursors / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D011498:Protein Precursors