This study investigated the relationship between a cathepsin K (CTSK) gene mutation and the pathogenesis of pycnodysostosis in a Chinese patient. A typical pycnodysostosis case and 30 healthy controls were enrolled into the study. Genomic DNA was extracted from blood samples taken from the patient and controls, and the encoding exons of CTSK were amplified and sequenced. Sequencing of the CTSK gene revealed homozygosity for a novel missense mutation in the pycnodysostosis patient, predicting the amino acid exchange from glutamine to proline at position 187 (Q187P). This point mutation in exon 5 of the CTSK gene results in the typical clinical features found in Chinese patients with pycnodysostosis. No similar changes in the CTSK gene sequences were found in the healthy controls.