A novel mutation in the HPGD gene causing primary hypertrophic osteoarthropathy with digital clubbing in a Pakistani family

Primary hypertrophic osteoarthropathy (PHO) is a congenital multisystemic entity characterized by three major clinical symptoms: pachydermia, periostosis, and digital clubbing. Recently it has been reported that pathogenic mutations in two genes are known to be associated with PHO: HPGD and SLCO2A1. In the present study, a five-generation consanguineous Pakistani family harboring primary hypertrophic osteoarthropathy in autosomal-recessive pattern was ascertained. Whole genome single nucleotide polymorphisms (SNPs) genotyping and sequence analysis revealed a novel homozygous missense mutation (c.577T?C) of the human HPGD gene in all affected members of the family. The study presented here demonstrate the first case of primary hypertrophic osteoarthropathy reported in Pashtun population.