title: A novel mutation (R122Q) in the cathepsin K gene in a Chinese child with Pyknodysostosis.
abstract: BACKGROUND
  Pyknodysostosis (OMIM 265800) is a rare, autosomal recessive sclerosing skeletal dysplasia as a consequence of the diminished capacity of osteoclasts to degrade organic bone matrix. Pyknodysostosis is caused by mutation in the cathepsin K (CTSK) gene. Up to date, 34 different CTSK mutations have been identified in patients with Pyknodysostosis; however, only one mutation was previously identified in a Chinese patient. The objective of this study was to characterize the clinical manifestations and features of Pyknodysostosis and identify the mutation of the causative gene in a Chinese family with Pyknodysostosis.
  
  
  METHODS
  We investigated a non-consanguineous Chinese family in which an 11-year-old child was affected with Pyknodysostosis. Altogether, 203 persons, including the affected individual, his parents and 200 healthy donors, were recruited and genomic DNA was extracted. All 8 exons of the CTSK gene, including the exon-intron boundaries, were amplified and sequenced directly.
  
  
  RESULTS
  The proband displayed a novel homozygous missense mutation c.365G>A in exon 4 of the CTSK gene. This mutation leads to the substitution of the arginine at position 122 by glutamine (R122Q) in cathepsin K. The parents were heterozygous for this gene mutation, and the mutation was not found in the 200 unrelated controls.
  
  
  CONCLUSIONS
  Our study suggests that the novel missense mutation c.365G>A (R122Q) in exon 4 of CTSK gene was responsible for Pyknodysostosis in the Chinese family.
authors.affiliation: Metabolic Bone Disease and Genetic Research Unit, Department of Osteoporosis and Bone Diseases, Shanghai Jiao Tong University affiliated with the Sixth People's Hospital, 600 Yi-Shan Rd., Shanghai 200233, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zheng
authors.forename: Zeng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jin-Wei
authors.initials: JW
authors.lastname: He
authors.forename: Wen-Zhen
authors.initials: WZ
authors.lastname: Fu
authors.forename: Zhen-Lin
authors.initials: ZL
authors.lastname: Zhang
mesh_terms: D044466:Asian People / Q000235:genetics; D056657:Cathepsin K / Q000235:genetics*; D002648:Child; D005091:Exons; D005260:Female; D006720:Homozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D058631:Pycnodysostosis / Q000209:etiology / Q000235:genetics*
chemical_list: C534130:CTSK protein, human; D056657:Cathepsin K