Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency.
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Gelb BD, Shi GP, Chapman HA, Desnick RJ
Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency.
Science. 1996 Aug 30;273(5279):1236-8.
- PubMed ID
- 8703060 [ View in PubMed]
- Abstract
Pycnodysostosis, an autosomal recessive osteochondrodysplasia characterized by osteosclerosis and short stature, maps to chromosome 1q21. Cathepsin K, a cysteine protease gene that is highly expressed in osteoclasts, localized to the pycnodysostosis region. Nonsense, missense, and stop codon mutations in the gene encoding cathepsin K were identified in patients. Transient expression of complementary DNA containing the stop codon mutation resulted in messenger RNA but no immunologically detectable protein. Thus, pycnodysostosis results from gene defects in a lysosomal protease with highest expression in osteoclasts. These findings suggest that cathepsin K is a major protease in bone resorption, providing a possible rationale for the treatment of disorders such as osteoporosis and certain forms of arthritis.