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

• Published in: Journal of investigative medicine Vol. 59; no. 2; pp. 277 - 280
• Main Authors: Toral-López, Jaime, Gonzalez-Huerta, Luz Maria, Sosa, Blanca, Orozco, Sócrates, González, Hugo Peláez, Cuevas-Covarrubias, Sergio A
• Format: Journal Article
• Language: English
• Published: 01.02.2011
• ISSN: 1708-8267
• DOI: 10.231/JIM.0b013e318202a9db

BACKGROUNDPycnodysostosis, 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.PURPOSETo describe the clinical, radiological, and molecular findings in a family with pycnodysostosis.METHODSThe CTSK gene was analyzed from genomic DNA in a nonconsanguinity Mexican family with 3 affected members with pycnodysostosis and 100 healthy controls.RESULTS AND INTERPRETATIONWe 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.