Genotype and phenotype characterization of primary hypertrophic osteoarthropathy type 2 and chronic enteropathy associated with SLCO2A1: Report of two cases and literature review

Abstract

Autosomal recessive type 2 primary hypertrophic osteoarthropathy (PHOAR2) and chronic enteropathy associated with SLCO2A1 (CEAS) are two entities caused by pathogenic variants (PVs) in the SLCO2A1 gene that can coexist or occur independently from one another. We report two cases of PHOAR2 in Mexico with concomitant CEAS and conducted a review of the literature of the reported cases of PHOAR2 and/or CEAS to analyze the relationship between their genotype and phenotype presentation. The patients from our Institution with classical PHOAR2 phenotype and CEAS, harbored SLCO2A1 c.547G > A and c.1768del variants. We reviewed 232 cases, of which 86.6% were of Asian origin, and identified 109 different variants in SLCO2A1. Intron 7, exon 13, and exon 4 were predominantly affected. The two most common PVs were c.940 + 1G > A and c.1807C > T. We found a statistically significant association between SLCO2A1 variants located in intron 7, exons 12, and 13 and the development of CEAS. Missense variants were more frequent in isolated PHOAR2, while a greater proportion of protein‐truncating variants (PTVs) were found in CEAS. Further investigation is imperative to elucidate the underlying pathophysiological mechanisms associated with CEAS, thereby facilitating the identification of effective therapeutic interventions.

Comprehensive Treatment of a Rare Case of Complete Primary Pachydermoperiostosis with Large Facial Keloid Scars: A Case Report and Literature Review

“…In 1935, three French dermatologists, Touraine et al [5], recognized this condition as a familial disorder with three forms: complete (periostosis and pachyderma), incomplete (without pachyderma), and the forme fruste (pachydermia with minimal skeletal changes) [2]. PDP is reportedly related to mutations in the HPGD (encoding 15-hydroxyprostaglandin dehydrogenase) or SLCO2A1 (encoding solute carrier organic anion transporter family member 2A1) genes [6][7][8][9][10], which lead to impaired prostaglandin E2 degradation, thus elevating prostaglandin E2 levels [11]. However, the other causes of PDP are still unclear.…”