Takagi Masaki, Shinohara Hiroyuki, Narumi Satoshi, Nishimura Gen, Hasegawa Yukihiro, Hasegawa Tomonobu
Department of Pediatrics, Keio University School of Medicine, Tokyo, Japan.
Department of Endocrinology and Metabolism, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan.
Am J Med Genet A. 2015 Jul;167(7):1627-31. doi: 10.1002/ajmg.a.37051. Epub 2015 Apr 9.
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.
大多数成骨不全症（OI）病例是由COL1A1或COL1A2中的杂合突变引起的，这两个基因分别编码两种I型前胶原α链，即proα1（I）和proα2（I）。我们报告了一例独特的严重OI病例，该患者是致死性II型OI的长期幸存者，而非进行性变形的III型，原因是位于同一等位基因上的COL1A2中的甘氨酸残基发生了双重替换（p.Gly208Glu和p.Gly235Asp）。据我们所知，这是同一等位基因上存在双重COL1A2甘氨酸替换突变患者的首个实例。我们首次表明，位于氨基末端三螺旋区域附近的双重COL1A2甘氨酸替换突变，单独来看可能导致轻度OI，但合并在一起会导致严重OI。
