Pachydermoperiostosis in an African patient caused by a Chinese/Japanese SLCO2A1 mutation—Case report and review of literature

• Published in: Seminars in arthritis and rheumatism Vol. 43; no. 4; pp. 566 - 569
• Main Authors: Madruga Dias, João A.C., MD, Rosa, Rita S., MD, Perpétuo, Inês, MSc, Rodrigues, Ana M., MD, Janeiro, André, MSc, Costa, Maria M., MD, Gaião, Luís, MD, Pereira da Silva, José A., MD, Fonseca, João E., PhD, Miltenberger-Miltenyi, Gabriel, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2014
• Subjects: Adult; African patient; corrective eye surgery; Eyelids - surgery; Hand - diagnostic imaging; homozygozity; HPGD; Humans; Knee - diagnostic imaging; Male; Mutation; Organic Anion Transporters - genetics; Osteoarthropathy, Primary Hypertrophic - diagnostic imaging; Osteoarthropathy, Primary Hypertrophic - genetics; Osteoarthropathy, Primary Hypertrophic - surgery; Pachydermoperiostosis; Radiography; Rheumatology; SLCO2A1; Treatment Outcome; mutation; HPGD; Pachydermoperiostosis; corrective eye surgery; SLCO2A1; African patient; homozygozity
• ISSN: 0049-0172; 1532-866X
• DOI: 10.1016/j.semarthrit.2013.07.015

Abstract Objectives Pachydermoperiostosis is a rare clinical entity characterized by skin thickening of the forehead, eyelids, and hands, digital clubbing, and periostosis. Two genes have been associated, HPGD and recently SLCO2A1. We present a detailed clinical and genetic description of an African pachydermoperiostosis patient with a SLCO2A1 mutation. Methods Standard clinical and laboratory evaluation was carried out. Genetic screening was done with PCR followed by direct sequencing. We discuss the clinical features and known mutations of previously reported cases identified through a PubMed literature review. Results The clinical findings showed special features, including exuberant knee effusions and an extraordinary good response on surgery of the blepharoptosis. We found a splice site mutation in the SLCO2A1 gene in homozygous form: c.940+1G>A. This mutation was previously reported only in 1 Chinese and 3 Japanese cases and was considered as a founder mutation in Japan. Beside our case, only one other patient in the literature carried this mutation in homozygous condition, but with different main clinical symptoms. Conclusions Our case demonstrates phenotypic heterogeneity of PDP even between homozygous carriers of the same mutation, suggesting further modifiers. Besides, it shows that this rare SLCO2A1 mutation is not exclusively present in East-Asia, but can occur in various ethnicities, with different origin, thus the incidence is probably underestimated.