Background: Primary hypertrophic osteoarthropathy (PHO), also called pachydermoperiostosis is characterized by digital clubbing, pachyderma, and periostosis and the precise incidence and prevalence are still unknown. PHO has been thought to be genetically heterogeneous and both autosomal dominant and autosomal recessive patterns have been suggested. In 2008, homozygous mutations in hydroxyprostaglandin dehydrogenase (HPGD), which encodes 15-hydroxyprostaglandin dehydrogenase (15-PGDH) were identified as a cause of PHO. More recently homozygous mutations in solute carrier organic anion transporter family, member 2A1 (SLCO2A1), the gene encoding the prostaglandin transporter were also identified in 3 Chinese families with PHO. Although as a result of studies that followed, knowledge of the pathomechanism of PHO has greatly improved that increased levels of prostaglandin E2 (PGE2) due to the failure of its degradation are involved, more cases and their genetic backgrounds are needed for the comprehensive understanding of this disease.
Clinical case: The 62-year-old Asian proband, who was born to healthy nonconsanguineous parents visited our clinic for genetic counseling of his son. At 19 years of age, the patient presented with enlarged hand and foot, knee joints swelling and pain and then was referred to neurosurgeon for suspicious of acromegaly. He got hypophysectomy but revealed no tumor lesion in the specimen. Attention was arouse only after periosteal thickening was noticed in the carpal, phalangeal, radial and ulnar simple X-ray, indicating PHO as well as facial furrowing. His two younger brothers also showed similar clinical features and we diagnosed them as PHO. Genetic analyses of the three siblings showed no abnormality in HPGD gene. However, we found a novel mutation in the SLCO2A1 gene as well as a known polymorphism in three affected siblings and none in his son who seems to be normal in appearance.
Conclusion: Here we add one more inactivating mutation in SLCO2A1 gene that causes PHO. This novel heterozygous mutation broadens the allelic spectrum of SLCO2A1 mutations. Further clinical study will be needed in order to validate the genotype-phenotype correlations and to develop any therapeutic options of PHO in future. The study of inherited monogenic diseases has contributed greatly to our mechanistic understanding of pathogenic mutations and gene regulation and has provided tremendous knowledge toward the common goal of developing methods for the early diagnosis and treatment of common disorders.
|