Lack of cyclophilin B in osteogenesis imperfecta with normal collagen folding.
Lack of cyclophilin B in osteogenesis imperfecta with normal collagen folding.
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DOI：
10.1056/nejmoa0907705
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发表时间：
2010-02-11
期刊：
影响因子：
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通讯作者：
Marini JC
中科院分区：
文献类型：
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作者：
Barnes AM;Carter EM;Cabral WA;Weis M;Chang W;Makareeva E;Leikin S;Rotimi CN;Eyre DR;Raggio CL;Marini JC
成骨不全症是一种导致骨骼脆弱的遗传性疾病。I型胶原的突变导致常染色体显性成骨不全，而胶原脯氨酰3-羟化复合物（软骨相关蛋白[CRTAP]和脯氨酰3-羟化酶1 [P3 H1]）的两种组分中的任一种突变导致常染色体隐性成骨不全伴根状肌节（上肢和下肢近端节段缩短）和延迟的胶原折叠。我们确定了两个兄弟姐妹谁有隐性成骨不全无根状茎。他们在肽基脯氨酰异构酶B基因（PPIB）中有一个纯合起始密码子突变，导致缺乏亲环蛋白B（CyPB），这是复合物的第三种成分。先证者的胶原蛋白具有正常的胶原蛋白折叠和正常的脯氨酰3-羟基化，这表明CyPB不是唯一的肽基脯氨酰顺反异构酶，其催化胶原蛋白折叠中的限速步骤，如目前认为的那样。
Osteogenesis imperfecta is a heritable disorder that causes bone fragility. Mutations in type I collagen result in autosomal dominant osteogenesis imperfecta, whereas mutations in either of two components of the collagen prolyl 3-hydroxylation complex (cartilage-associated protein [CRTAP] and prolyl 3-hydroxylase 1 [P3H1]) cause autosomal recessive osteogenesis imperfecta with rhizomelia (shortening of proximal segments of upper and lower limbs) and delayed collagen folding. We identified two siblings who had recessive osteogenesis imperfecta without rhizomelia. They had a homozygous start-codon mutation in the peptidyl-prolyl isomerase B gene (PPIB), which results in a lack of cyclophilin B (CyPB), the third component of the complex. The proband’s collagen had normal collagen folding and normal prolyl 3-hydroxylation, suggesting that CyPB is not the exclusive peptidyl-prolyl cis–trans isomerase that catalyzes the rate-limiting step in collagen folding, as is currently thought.