title: Novel CTSK mutation resulting in an entire exon 2 skipping in a Thai girl with pycnodysostosis.
abstract: 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.
authors.affiliation: Center of Excellence for Medical Genetics, Department of Pediatrics, Chulalongkorn University, Bangkok, Thailand; Excellence Center for Medical Genetics, King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand.
authors.forename: Pattarapa
authors.initials: P
authors.lastname: Utokpat
authors.forename: Wipa
authors.initials: W
authors.lastname: Panmontha
authors.forename: Siraprapa
authors.initials: S
authors.lastname: Tongkobpetch
authors.forename: Kanya
authors.initials: K
authors.lastname: Suphapeetiporn
authors.forename: Vorasuk
authors.initials: V
authors.lastname: Shotelersuk
mesh_terms: D056657:Cathepsin K / Q000235:genetics* / Q000378:metabolism; D002648:Child; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006720:Homozygote; D006801:Humans; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction; D058631:Pycnodysostosis / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism
chemical_list: D004247:DNA; C534130:CTSK protein, human; D056657:Cathepsin K
keywords: CTSK; cathepsin K; exon skipping; mutation; pycnodysostosis