Barnes Aileen M, Chang Weizhong, Morello Roy, Cabral Wayne A, Weis MaryAnn, Eyre David R, Leikin Sergey, Makareeva Elena, Kuznetsova Natalia, Uveges Thomas E, Ashok Aarthi, Flor Armando W, Mulvihill John J, Wilson Patrick L, Sundaram Usha T, Lee Brendan, Marini Joan C
National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
N Engl J Med. 2006 Dec 28;355(26):2757-64. doi: 10.1056/NEJMoa063804.
Classic osteogenesis imperfecta, an autosomal dominant disorder associated with osteoporosis and bone fragility, is caused by mutations in the genes for type I collagen. A recessive form of the disorder has long been suspected. Since the loss of cartilage-associated protein (CRTAP), which is required for post-translational prolyl 3-hydroxylation of collagen, causes severe osteoporosis in mice, we investigated whether CRTAP deficiency is associated with recessive osteogenesis imperfecta. Three of 10 children with lethal or severe osteogenesis imperfecta, who did not have a primary collagen defect yet had excess post-translational modification of collagen, were found to have a recessive condition resulting in CRTAP deficiency, suggesting that prolyl 3-hydroxylation of type I collagen is important for bone formation.
典型成骨不全症是一种与骨质疏松和骨脆性相关的常染色体显性疾病，由I型胶原蛋白基因的突变引起。长期以来人们一直怀疑存在该疾病的隐性形式。由于软骨相关蛋白（CRTAP）的缺失会导致小鼠出现严重的骨质疏松，而CRTAP是胶原蛋白翻译后脯氨酰3-羟基化所必需的，因此我们研究了CRTAP缺乏是否与隐性成骨不全症有关。在10名患有致死性或严重性成骨不全症的儿童中，有3名儿童没有原发性胶原蛋白缺陷，但存在胶原蛋白过度的翻译后修饰，结果发现他们患有导致CRTAP缺乏的隐性疾病，这表明I型胶原蛋白的脯氨酰3-羟基化对骨形成很重要。
