Pycnodysostosis, a lysosomal disease caused by cathepsin K deficiency.
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.
Gelb
B D
BD
Department of Human Genetics and Division of Pediatric Cardiology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Shi
G P
GP
Chapman
H A
HA
Desnick
R J
RJ
D000595:Amino Acid Sequence; D001483:Base Sequence; D001857:Bone Matrix / Q000378:metabolism; D001862:Bone Resorption; D056657:Cathepsin K; D002403:Cathepsins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D018388:Codon, Terminator; D015226:Dinucleoside Phosphates / Q000235:genetics; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000201:enzymology / Q000235:genetics*; D008247:Lysosomes / Q000201:enzymology*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010009:Osteochondrodysplasias / Q000201:enzymology / Q000235:genetics*; D010010:Osteoclasts / Q000201:enzymology*; D014162:Transfection
D056657:Cathepsin K; D002403:Cathepsins; D018388:Codon, Terminator; D015226:Dinucleoside Phosphates; C015772:CpG dinucleotide; C028217:cathepsin S; C534130:CTSK protein, human