Novel compound heterozygous mutations in the cathepsin K gene in Japanese female siblings with pyknodysostosis
Novel compound heterozygous mutations in the cathepsin K gene in Japanese female siblings with pyknodysostosis
复制标题
患有致密性骨性骨质疏松症的日本女性同胞中组织蛋白酶 K 基因的新型复合杂合突变
DOI：
10.1159/000336581
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发表时间：
2012
期刊：
影响因子：
1.1
通讯作者：
Ishiguro N
中科院分区：
文献类型：
--
作者：
Matsushita M;Kitoh H;Kaneko H;Mishima K;Itoh Y;Hattori T;Ishiguro N
我们报告的女性同胞与固缩骨发育不全谁表现出共同的临床和影像学特征，包括不成比例的身材矮小，牙齿异常，骨密度增加，开放的，和肢端骨质溶解。组织蛋白酶K（CTSK）基因的序列分析表明，在受影响的兄弟姐妹中存在复合杂合突变（935 C> T，A277 V和489 G> C，R122 P），在其父母中存在杂合突变。前一种错义突变已在6例无关患者中报道，后一种似乎是一种新的突变。CTSK基因的原子模型评估显示，R122 P突变体可以破坏与软骨素4-硫酸酯的氢键结合，导致组织蛋白酶K的胶原降解活性降低。
We report on female siblings with pyknodysostosis who showed common clinical and radiographic features including disproportionate short stature, dental abnormalities, increased bone density, open fontanelle, and acroosteolysis. Sequence analysis of the cathepsin K (CTSK) gene demonstrated compound heterozygous mutations (935 C> T, A277V and 489 G> C, R122P) in the affected siblings and a heterozygous mutation in their parents. The former missense mutation has previously been reported in 6 unrelated patients, and the latter seemed to be a novel mutation. Atomic model assessment of the CTSK gene revealed that the R122P mutant could disrupt hydrogen bonds binding with chondroitin 4-sulfate leading to a decrease in the collagen-degrading activity of cathepsin K.