Background Deficiency of cathepsin K (CTSK), a lysosomal cysteine protease, has been shown earlier as a cause of an autosomal recessive osteosclerotic skeletal dysplasia pycnodysostosis. The objective of the present study was to identify the potential sequence variants in CTSK gene in a large consanguineous Pakistani family with pycnodysostosis.
Methods Genotyping of 4 affected and 6 unaffected members of the family was performed using polymorphic microsatellite markers linked to CTSK gene on chromosome 1q21. To screen for pathogenic mutation, exons and splice junctions of CTSK gene were polymerase chain reaction amplified from genomic DNA and sequenced directly in an automated DNA sequencer.
Results Microsatellite analysis showed linkage of the family to CTSK gene on chromosome 1q21. Sequence analysis revealed a novel missense mutation c.728G>A (p.G243E) in exon 6 of the CTSK gene.
Conclusions A novel missense mutation was identified in CTSK gene in a Pakistani family with 5 individuals affected with autosomal recessive pycnodysostosis