SLCO2A1 – Chronic Enteropathy Associated with SLCO2A1 Gene

Chronic enteropathy associated with SLCO2A1 gene (CEAS) is an autosomal recessive disorder caused by biallelic loss-of-function variants in SLCO2A1, encoding a prostaglandin E₂ transporter (PGT) ([PMID:26539716]). Patients develop persistent nonspecific small intestinal ulcers, chronic anemia, hypoalbuminemia, and protein-losing enteropathy, often misdiagnosed as Crohn’s disease.

Genetic studies have identified over 40 unrelated probands with CEAS in Japanese, Chinese, and other populations ([PMID:26539716]; [PMID:38755710]). A novel homozygous splice-altering variant, c.929A>G (p.Asp310Gly), was reported in a Chinese patient and confirmed by Sanger sequencing ([PMID:38862970]). Parental consanguinity in multiple families and recessive segregation support autosomal recessive inheritance.

The variant spectrum encompasses approximately 30–35 pathogenic alleles, including missense (e.g., c.547G>A (p.Gly183Arg)), splicing (c.940+1G>A), nonsense (p.Ser506Ter), and frameshift changes, with a Japanese founder splice-site mutation (c.940+1G>A) recurring in cohorts ([PMID:26539716]).

Functional assays in Xenopus laevis oocytes show that 10 of 11 CEAS-associated SLCO2A1 mutations markedly reduce PGE₂ transport capacity ([PMID:35877192]). In vitro minigene models and qPCR confirm that c.929A>G causes exon 7 skipping and abolishes normal transcript expression in patient tissues ([PMID:38862970]).

Clinically, CEAS patients present with chronic anemia, hypoalbuminemia, abdominal pain, diarrhea, and protein-losing enteropathy; >25% manifest primary hypertrophic osteoarthropathy features such as clubbing and periostosis ([PMID:29313109]).

Integration of genetic and functional data establishes loss-of-function of SLCO2A1 as the definitive cause of CEAS. Genetic testing for SLCO2A1 mutations is recommended in early-onset enteropathy with normal inflammatory markers unresponsive to conventional therapies. Key take-home: Biallelic SLCO2A1 mutations drive CEAS via defective prostaglandin transport, underpinning precision diagnosis and genetic counseling.

References

• PLoS Genetics • 2015 • A Hereditary Enteropathy Caused by Mutations in the SLCO2A1 Gene, Encoding a Prostaglandin Transporter. PMID:26539716
• Journal of Gastroenterology • 2018 • Clinical features of chronic enteropathy associated with SLCO2A1 gene: a new entity clinically distinct from Crohn's disease. PMID:29313109
• Journal of Gastroenterology and Hepatology • 2022 • Functional analysis of mutant SLCO2A1 transporters found in patients with chronic enteropathy associated with SLCO2A1. PMID:35877192
• Orphanet Journal of Rare Diseases • 2024 • A novel variant in the SLCO2A1 gene in a Chinese patient with chronic gastroenteropathy and primary hypertrophic osteoarthropathy. PMID:38862970
• Orphanet Journal of Rare Diseases • 2024 • Clinical and genetic characteristics of Chinese patients diagnosed with chronic enteropathy associated with SLCO2A1 gene. PMID:38755710

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