Novel Compound Heterozygous Mutations in the Cathepsin K Gene in Japanese Female Siblings with Pyknodysostosis.
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Matsushita M, Kitoh H, Kaneko H, Mishima K, Itoh Y, Hattori T, Ishiguro N
Novel Compound Heterozygous Mutations in the Cathepsin K Gene in Japanese Female Siblings with Pyknodysostosis.
Mol Syndromol. 2012 Apr;2(6):254-258. Epub 2012 Mar 6.
- PubMed ID
- 22822386 [ View in PubMed]
- Abstract
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.