title: Severe osteogenesis imperfecta caused by double glycine substitutions near the amino-terminal triple helical region in COL1A2.
abstract: Most cases of osteogenesis imperfecta (OI) are caused by heterozygous mutations in COL1A1 or COL1A2, the genes encoding the two type I procollagen alpha chains, proα1 (I) and proα2 (I). We report on a unique case of severe OI, a long term survivor of lethal type II OI, rather than progressively deforming type III, due to double substitutions of glycine residues in COL1A2 (p.Gly208Glu and p.Gly235Asp), located on the same allele. To the best of our knowledge, this is the first example of a patient with double COL1A2 glycine substitution mutations on the same allele. We show for the first time that double COL1A2 glycine substitution mutations located near the amino-terminal triple helical region, which individually are likely to result in mild OI, cause severe OI in combination.
authors: Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.|Department of Endocrinology and Metabolism, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors: Masaki
authors: M
authors: Takagi
authors: Department of Endocrinology and Metabolism, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors: Hiroyuki
authors: H
authors: Shinohara
authors: Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
authors: Satoshi
authors: S
authors: Narumi
authors: Department of Radiology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors: Gen
authors: G
authors: Nishimura
authors: Department of Endocrinology and Metabolism, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
authors: Yukihiro
authors: Y
authors: Hasegawa
authors: Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
authors: Tomonobu
authors: T
authors: Hasegawa
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D001483:Base Sequence; D024042:Collagen Type I / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005998:Glycine; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D008969:Molecular Sequence Data; D060885:Multiplex Polymerase Chain Reaction; D010013:Osteogenesis Imperfecta / Q000000981:diagnostic imaging* / Q000235:genetics*; D011859:Radiography
chemical_list: C000601279:COL1A2 protein, human; D024042:Collagen Type I; D005998:Glycine
keywords: double mutation; glycine; osteogenesis imperfect