Familial pycnodysostosis: identification of a novel mutation in the CTSK gene (cathepsin K).

Pycnodysostosis, an autosomal recessive skeletal dysplasia, is characterized by short stature, osteosclerosis, delayed cranial suture closure, hypoplastic mandible, acro-osteolysis, hypoplastic clavicle, and dental anomalies. The disorder is caused by CTSK gene defects, a gene localized on 1q21. To describe the clinical, radiological, and molecular findings in a family with pycnodysostosis. The CTSK gene was analyzed from genomic DNA in a nonconsanguinity Mexican family with 3 affected members with pycnodysostosis and 100 healthy controls. We identified the novel homozygous mutation c.908G>A within exon 8 of the CTSK gene. This missense mutation leads to the substitution of the amino acid glycine at position 303 by glutamic acid (G303E) in cathepsin K protease. No genotype/phenotype correlation was present in affected members of the family with pycnodysostosis.