Pycnodysostosis is a rare autosomal recessive skeletal dysplasia characterized by osteosclerosis, short stature, acro-osteolysis of the distal phalanges, bone fragility and skull deformities. Mutations in the cathepsin K (CTSK) gene, which encodes a lysosomal cysteine protease highly expressed in osteoclasts, have been found to be responsible for the disease. We identified a Thai girl with pycnodysostosis. Her parents were first cousins. Polymerase chain reaction sequencing of the entire coding regions of CTSK of the proband's complementary DNA revealed that the whole exon 2 was skipped. We subsequently amplified exon 2 using genomic DNA, which showed that the patient was homozygous for a c.120G>A mutation. The mutation was located at the last nucleotide of exon 2. Its presence was confirmed by restriction enzyme analysis using BanI. The skipping of exon 2 eliminates the normal start codon. The mutation has never been previously reported, thus the current report expands the CTSK mutational spectrum.
Keywords: CTSK; cathepsin K; exon skipping; mutation; pycnodysostosis.
© 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.