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.
摘要：
常染色体隐性遗传2型原发性肥厚性骨关节病（PHOAR2）和与SLCO2A1（CEAS）相关的慢性肠病是由SLCO2A1基因中的致病性变体（PV）引起的两个实体，它们可以共存或彼此独立发生。我们报告了墨西哥的2例PHOAR2合并CEAS的病例，并对报道的PHOAR2和/或CEAS病例进行了文献回顾，以分析其基因型和表型表现之间的关系。来自我们机构的具有经典PHOAR2表型和CEAS的患者，藏有SLCO2A1c.547G>A和c.1768del变体。我们回顾了232例，其中86.6%来自亚洲，并在SLCO2A1中鉴定出109种不同的变体。内含子7、外显子13和外显子4主要受到影响。两个最常见的PV是c.940+1G>A和c.1807C>T。我们发现位于内含子7、外显子12和13的SLCO2A1变体与CEAS的发展之间存在统计学上的显著关联。错义变体在分离的PHOAR2中更常见，而在CEAS中发现了更大比例的蛋白质截短变体（PTV）。进一步的研究是必要的阐明潜在的病理生理机制与CEAS相关，从而有助于确定有效的治疗干预措施。
