SLCO2A1 Research Articles

Complete pachydermoperiostosis (Touraine–Solente–Gole Syndrome) in a young Yemeni man

Pachydermoperiostosis (PDP) is a rare genodermatosis, caused by pathogenic variants in the 15-hydroxyprostaglandin dehydrogenase (HPGD) or Solute Carrier Organic Anion Transporter Family Member 2A1 (SLCO2A1) genes, affecting the skin and bones. It is frequently misdiagnosed as acromegaly due to its presentation, which includes digital clubbing, bone thickening, and deep skin creases on the forehead. We report the first Yemeni case of PDP in a 22-year-old man who displayed classic features: digital clubbing, pachydermia (thickening of the skin) with furrowing on the forehead and scalp, bone thickening (hyperostosis) of the fingers, toes, radius, ulna, tibia, and fibula, as well as hyperhidrosis and seborrhea. Although acromegaly was initially considered, the absence of other typical features led to a final diagnosis of PDP. PDP should be considered in patients presenting with acromegaloid features.

Characteristics of chronic enteropathy associated with SLCO2A1 gene (CEAS) in children, a unique type of monogenic very early-onset inflammatory bowel disease

Background Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a unique type of inflammatory bowel disease. CEAS is monogenic disease and is thought to develop from childhood, but studies on pediatric CEAS are scarce. We analyzed characteristics of pediatric CEAS.MethodsEleven patients diagnosed with CEAS at Seoul National University Children’s Hospital were identified and analyzed. Clinical data of patients were collected. Sanger sequencing of SLCO2A1 was performed on all patients.ResultsPatients were diagnosed at a median age of 16.0 years (IQR 11.0 ~ 20.0), and the median age at symptoms onset was only 4.0 years (IQR 2.5 ~ 6.0). Growth delay was observed at the time of diagnosis. Patients showed multiple ulcers or strictures in the small intestine, while the esophagus and colon were unaffected in any patients. Almost half of the patients underwent small intestine resection. The major laboratory features of pediatric CEAS include iron deficiency anemia (IDA), hypoalbuminemia, and near-normal levels of C-reactive protein (CRP). Two novel mutations of SLCO2A1 were identified. The most prevalent symptoms were abdominal pain and pale face. None of the immunomodulatory drugs showed a significant effect on CEAS.ConclusionsPediatric CEAS typically develop from very young age, suggesting it as one type of monogenic very early onset inflammatory bowel disease. CEAS can cause growth delay in children but there is no effective treatment currently. We recommend screening for SLCO2A1 mutations to pediatric patients with chronic IDA from a young age and small intestine ulcers without elevation of CRP levels.

A novel variant in the SLCO2A1 gene in a Chinese patient with chronic gastroenteropathy and primary hypertrophic osteoarthropathy

BackgroundChronic enteropathy associated with SLCO2A1 gene (CEAS) results from loss-of-function variants in SLCO2A1, which encodes the prostaglandin transporter (PGT). CEAS follows an autosomal recessive inheritance pattern. To date, approximate 30 pathogenic variants have been reported in CEAS.MethodsWe performed whole exome sequencing (WES) to screen for potential pathogenic variants in a patient suspected of having CEAS, and confirmed a variant in SLCO2A1 using Sanger sequencing. We established an in vitro minigene model to compare splicing between wild type (WT) and mutant transcripts. Quantitative polymerase chain reaction (qPCR) was used to evaluate SLCO2A1 transcription in the stomach and colon tissues from the patient and a healthy control (HC). The transcripts were further cloned and sequenced.ResultsThe patient had a novel, homozygous, recessive c.929A > G variant in exon 7 of SLCO2A1, which has not been previously reported in CEAS or PHO. This variant altered splicing, resulting in an exon 7‐truncated transcript lacking 16 bases. No normal transcript was detected in the patient’s stomach or colon tissue. qPCR also showed significantly decreased SLCO2A1 transcription compared to HC.ConclusionA previously unreported variant caused defective SLCO2A1 splicing and reduced mRNA levels in a patient with CEAS and PHO. This research enhances understanding of CEAS and PHO pathophysiology and aids genetic counseling and diagnosis.

Pathogenesis of chronic enteropathy associated with the SLCO2A1 gene: Hypotheses and conundrums.

Chronic enteropathy associated with the SLCO2A1 gene (CEAS) is a complex gastroenterological condition characterized by multiple ulcers in the small intestine with chronic bleeding and protein loss. This review explores the potential mechanisms underlying the pathogenesis of CEAS, focusing on the role of SLCO2A1-encoded prostaglandin transporter OATP2A1 and its impact on prostaglandin E2 (PGE2) levels. Studies have suggested that elevated PGE2 levels contribute to mucosal damage, inflammation, and disruption of the intestinal barrier. The effects of PGE2 on macrophage activation and Maxi-Cl channel functionality, as well as its interaction with nonsteroidal anti-inflammatory drugs play crucial roles in the progression of CEAS. Understanding the balance between its protective and pro-inflammatory effects and the complex interactions within the gastrointestinal tract can shed light on potential therapeutic targets for CEAS and guide the development of novel, targeted therapies.

Clinical and genetic characteristics of Chinese patients diagnosed with chronic enteropathy associated with SLCO2A1 gene

Background and aimsChronic enteropathy associated with SLCO2A1 gene is a rare intestinal disease caused by loss-of-function SLCO2A1 mutations, with clinical and genetic characteristics remaining largely unknown, especially in Chinese patients. This study aims to reveal clinical and genetic features of Chinese CEAS patients, highlighting the previously unreported or unemphasized characteristics.MethodsWe enrolled 12 Chinese patients with chronic enteropathy associated with SLCO2A1 gene admitted to Peking Union Medical College Hospital from January 2018 to December 2022. Clinical and genetic data of these patients were collected and analyzed.Results58.3% of patients were male, who also had primary hypertrophic osteoarthropathy, whereas female patients did not have primary hypertrophic osteoarthropathy. Apart from common symptoms associated with anemia and hypoalbuminemia, abdominal pain, ileus, diarrhea, and hematochezia were present. 4 of the 5 female patients had early-onset amenorrhea, though the causal relationship remained to be clarified. Endoscopy and computed tomography enterography revealed that lesions can occur in any part of the digestive tract, most commonly in the ileum. Pathology showed multiple superficial ulcers with adjacent vascular dilatation, and loss of SLCO2A1 expression, particularly in gastrointestinal vascular endothelial cells. Genetic analysis confirmed SLCO2A1 mutations in all patients and identified 11 new SLCO2A1 variants for CEAS.ConclusionsThis study reports new clinical, pathological, and genetic findings in 12 Chinese patients with chronic enteropathy associated with SLCO2A1 gene. This study provides insights into the pathogenesis of this disease. However, studies with larger sample sizes and more in-depth mechanism research are still required.

Modulation of prostaglandin transport activity of SLCO2A1 by annexin A2 and S100A10.

Solute carrier organic anion transporter family member 2A1 (SLCO2A1) is a prostaglandin (PG) transporter and serves as the osmosensitive ATP-permeable maxi-anion channel (Maxi-Cl). Since a heterotetrameric complex of annexin A2 (ANXA2) and S100A10 is obligatory for the channel activity, the present study aimed to determine if they regulate SLCO2A1-mediated PG transport. This study examined PGE2 uptake and ATP release in Anxa2 and/or S100a10 knockout (KO) murine breast C127 cells. Deletion of Slco2a1 decreased PGE2-d4 uptake by wild-type (WT) cells in an isotonic medium (290 mosmol/kgH2O). Decreased osmolarity (135 mosmol/kgH2O) stimulated ATP release but did not affect PGE2 uptake kinetics, showing Km (1,280 nM) and Vmax (10.38 pmol/15 s/mg protein) similar to those in isotonic medium (1,227 nM and 10.65 pmol/15 s/mg protein), respectively, in WT cells. Deletion of Anxa2 associated with loss of S100a10 diminished SLCO2A1-mediated ATP release and uncompetitively inhibited PGE2 uptake with lowered Km (376 nM) and Vmax (2.59 pmol/15 s/mg protein). Moreover, the immunoprecipitation assay confirmed the physical interaction of ANXA2 with SLCO2A1 in WT cells. Enforcement of ANXA2 expression to Anxa2 KO cells partially restored PGE2 uptake and increased Km (744.3 nM) and Vmax (9.07 pmol/15 s/mg protein), whereas the uptake clearance (Vmax/Km) did not change much regardless of ANXA2 expression. These results suggest that an ANXA2/S100A10 complex modulates PG transport activity but osmolality has little effect on it; therefore, the bound form of SLCO2A1, which functions as a PG transporter and Maxi-Cl, may exist regardless of changes in the cell volume.NEW & NOTEWORTHY A previous study indicated that the ANXA2/S100A10 complex represents the regulatory component of SLCO2A1-mediated Maxi-Cl channel activity. The present study showed that apparent PGE2 uptake by C127 cells was osmoinsensitive and uncompetitively inhibited by loss of ANXA2 expression, demonstrating that ANXA2 is a regulatory factor of SLCO2A1-mediated PG transport activity.

HYPERTROPHIC OSTEOARTHROPATHY IN A PATIENT WITH HETEROZYGOUS MUTATION IN THE SLCO2A1 GENE: A CASE REPORT

Hypertrophic osteoarthropathy (HOA) is a condition characterized by aberrant skin and osseous tissue proliferation in the distal extremities. Mutations in the 15-hydroxyprostaglandin dehydrogenase gene (HPGD) and the soluble carrier organic anion carrier family member 2A1 gene (SLCO2A1) were associated with primary HOA. Secondary HOA, which is also called as 'hypertrophic pulmonary osteoarthropathy' is responsible for 95-97% of cases. Herein, we present a 19-year-old female patient with primary HOA and heterozygous mutation in the SLCO2A1 gene.

Atypical primary hypertrophic osteoarthropathy diagnosed with a novel SLCO2A1 gene mutation

AbstractPrimary hypertrophic osteoarthropathy (HOA) is a rare condition with no identifiable cause, accounting for 3%–5% of all HOA cases. It is challenging to identify incomplete primary HOA, which can be misdiagnosed as other hypertrophic periostitis diseases. At least two of the four criteria set by Borochowitz and Rimoin (1990) must be present to diagnose primary HOA. Diagnostic difficulties due to incomplete or atypical manifestations are common. We present a case of incomplete primary PHOA at Hanoi Medical University Hospital in Vietnam. A 37-year-old male presented with ankle joint pain for nearly four years. X-ray and magnetic resonance imaging showed periostitis in the tibias and fibulas, which could not exclude Camurati–Engelmann disease. Finally, gene sequencing on the Illumina MiSeq system identified a missense mutation (c.295C>T) in the solute carrier organic anion transporter family member 2A1 (SLCO2A1) gene on chromosome 3. Our case report and literature review aim to improve specialists' understanding of incomplete primary HOA and reduce the frequency of missed diagnoses.

Primary hypertrophic osteoarthropathy: genetics, clinical features and management.

Primary hypertrophic osteoarthropathy (PHO) is a genetic disorder mainly characterized by clubbing fingers, pachydermia and periostosis. Mutations in the HPGD or SLCO2A1 gene lead to impaired prostaglandin E2 (PGE2) degradation, thus elevating PGE2 levels. The identification of the causative genes has provided a better understanding of the underlying mechanisms. PHO can be divided into three subtypes according to its pathogenic gene and inheritance patterns. The onset age, sex ratio and clinical features differ among subtypes. The synthesis and signaling pathways of PGE2 are outlined in this review. Cyclooxygenase-2 (COX-2) is the key enzyme that acts as the rate-limiting step for prostaglandin production, thus COX-2 inhibitors have been used to treat this disease. Although this treatment showed effective results, it has side effects that restrain its use. Here, we reviewed the genetics, clinical features, differential diagnosis and current treatment options of PHO according to our many years of clinical research on the disease. We also discussed probable treatment that may be an option in the future.

Clinical and genetic characteristics of primary hypertrophic osteoarthropathy

Background. Primary hypertrophic osteoarthropathy is a rare genetically heterogeneous disease with three clinical variants. The classic one is a combination of hyperostosis, arthropathy and pachyderma and two variants with damage to only bone structures or pachyderma. Two genes responsible for the occurrence of primary hypertrophic osteoarthropathy have been identified: HPGD (debut age up to one year) and SLCO2A1 (debut in puberty and adolescence), whose products are involved in prostaglandin E2 metabolism. Two recurrent variants were identified in the HPGD gene: c.175_176delCT(p.Leu59fs) in patients from Europe and c.310_311delCT in patients from China. There were no clinical and genetic correlations in patients with different variants in the identified genes, which may be due to a small number of observations. The analysis of clinical manifestations in patients with newly identified variants or previously unidentified combinations of variants in a compound‑heterozygous state helps to understand the pathogenesis and prognosis of the course of the disease.Aim. To present the clinical and genetic characteristics of two Russian patients with primary hypertrophic osteoarthropathy caused by a newly identified combination of nucleotide variants in a compound‑heterozygous state in the HPGD and SLCO2A1 genes.Materials and methods. Clinical examination, radiography of the skeleton and chest, electrocardiography, echocardiography. Confirmation of the pathogenicity of the identified variants and clarification of the type of disease was carried out using automatic Sanger sequencing.Results. The clinical and genetic characteristics of two unrelated patients with primary hypertrophic osteoarthropathy caused by an undescribed combination of variants in the compound heterozygous state in the HPGD and SLCO2A1 genes were analyzed. In a patient with variants in the SLCO2A1 gene, the disease debuts at the age of 14 with deformities of the fingers, nails on the hands and feet, followed by the addition of burning pain in the distal parts of the arms and legs. At the age of 33, the examination revealed deformity of the fingers of the hands and feet by the type of drumsticks and nails by the type of watch glasses, enlargement of the knee joints, pronounced arthralgia. There were no signs of pachyderma. The new generation sequencing revealed two variants in the SLCO2A1 gene c.764G>A(p.Gly255Glu) in exon 6 and c.1333C>T(p.Arg445Cys) in exon 10. These variants were identified earlier in a compound‑heterozygous combination with other variants in patients with the classical phenotype of the disease, which were not present in the patient we observed. A feature of the case was pronounced hyperhidrosis and burning pain in the extremities, which may be due to stimulation of nociceptors in the musculoskeletal structures.Deformities of the fingers, nails of the hands and feet occurred in a patient with variants in the HPGD gene at 6 months. At the age of 9 years, a change in shape, stiffness and arthralgia of the knee and elbow joints without pachyderma were revealed. The identified variant with c.175_176delCT(p.Leu59fs) in this gene is often found in patients from European countries, and the other is c.1A>G(p.Met1?) discovered for the first time.Conclusion. The results allow us to conclude that when we found combinations of two variants in the HPGD and SLCO2A1 genes, there will be no pachyderma in the spectrum of clinical manifestations of primary hypertrophic osteoarthropathy. Sequencing of the new generation exome is the optimal diagnostic method.

Touraine-Solente-Gole syndrome: pathogenic variant in SLCO2A1 presented with polyarthralgia and digital clubbing

BackgroundPrimary Hypertrophic Osteoarthropathy (PHO), also known as Touraine-Solente-Gole Syndrome, is a rare, multisystemic autosomal recessive disorder caused by pathogenic variants in the 15-hydroxyprostaglandin dehydrogenase (HPGD) or Solute Carrier Organic Anion Transporter Family Member 2A1 (SLCO2A1) genes. However, autosomal dominant transmission has also been described in some families with incomplete penetrance. PHO usually starts in childhood or adolescence, presenting with digital clubbing, osteoarthropathy, and pachydermia. We described a complete form of the syndrome in a male patient with a homozygous variant in the SLCO2A1 gene (c.1259G > T).Case presentationA 20-year-old male was referred to our Pediatric Rheumatology Clinic with a five-year history of painful and swollen hands, knees, ankles and feet, prolonged morning stiffness and relief with non-steroidal antiinflammatory drugs. He also reported late onset facial acne and palmoplantar hyperhidrosis. Family history was irrelevant and parents were non-consanguineous. On clinical examination, he presented clubbing of the fingers and toes, moderate acne and marked facial skin thickening with prominent scalp folds. He had hand, knee, ankles and feet swelling. Laboratory investigations showed elevated inflammatory markers. Complete blood count, renal and hepatic function, bone biochemistry were normal, as well as immunological panel. Plain radiographs revealed soft tissue swelling, periosteal ossification and cortical thickening of the skull, phalanges, femur and toe acroosteolysis. Due to the absence of other clinical signs suggesting a secondary cause, we suspected PHO. A genetic study revealed a likely pathogenic variant, c.1259G > T(p.Cys420Phe), in homozygosity in the SLCO2A1 gene, thus confirming the diagnosis. The patient started oral naproxen with significant clinical improvement.ConclusionsPHO should be kept in the differential diagnosis of inflammatory arthritis affecting children, often misdiagnosed as Juvenile Idiopathic Arthritis (JIA). To the best of our knowledge, this is the second genetically confirmed case of PHO in a Portuguese patient (first variant c.644 C > T), both made at our department.

Eosinophilic enteritis requiring differentiation from chronic enteropathy associated with SLCO2A1 gene: A case report

Eosinophilic gastrointestinal disease (EGID) is a disorder characterized by infiltration of eosinophils causing mucosal damage and dysfunction of the gastrointestinal tract. The endoscopic findings of eosinophilic enteritis (EoN), an EGID variant, are nonspecific and occasionally difficult to diagnose. In contrast, chronic enteropathy associated with SLCO2A1 (CEAS) is a chronic persistent small intestinal disorder characterized by endoscopic findings such as multiple oblique and circular ulcers. We report the case of a 10-year-old boy who had suffered abdominal pain and fatigue for the preceding 6 mo. He was referred to our institute for investigation of suspected gastrointestinal bleeding because of severe anemia with hypoproteinemia and positive fecal human hemoglobin. The upper and lower gastrointestinal endoscopic findings were normal; however, double-balloon small bowel endoscopy showed multiple oblique and circular ulcers with discrete margins and mild constriction of the intestinal lumen in the ileum. The findings were highly consistent with CEAS, but urine prostaglandin metabolites were within normal limits, and no previously reported mutations in the SLCO2A1 gene were identified. Histological evaluation demonstrated moderate to severe eosinophilic infiltration localized to the small intestine suggesting a diagnosis of EoN. Clinical remission was maintained with montelukast and a partial elemental diet, but emergent surgery for bowel obstruction due to small intestinal stenosis was performed two years after the initial treatment. EoN should be considered in the differential diagnosis of CEAS-like small intestinal ulcerative lesions and normal urinary prostaglandin metabolite levels.

Homozygous Missense Variant in the Solute Carrier Organic Anion Transporter 2A1 (SLCO2A1) Gene Underlies Isolated Nail Clubbing.

Inherited isolated nail clubbing is a very rare Mendelian condition in humans, characterized by enlargement of the terminal segments of fingers and toes with thickened nails. Mutations in two genes have been reported to cause isolated nail clubbing in humans, which are the SLCO2A1 gene and the HPGD gene. An extended Pakistani family having two affected siblings born of unaffected consanguineous union was included in the study. Predominant isolated congenital nail clubbing (ICNC) without any other systemic abnormalities was observed, which we aimed to characterize at clinico-genetic level. Whole exome coupled with Sanger sequencing were employed to uncover the sequence variant as a cause of the disease. Furthermore, protein modeling was carried out to reveal the predicted possible effect of the mutation at the protein level. Whole exome sequencing data analysis revealed a novel biallelic sequence variant (c.155T>A; p.Phe52Tyr) in the SLCO2A1 gene. Further, Sanger sequencing analysis validated and confirmed the segregation of the novel variant in the entire family. Subsequently, protein modeling of the wild-type and mutated SLCO2A1 revealed broad-scale change, which might compromise the proteins' secondary structure and function. The present study adds another mutation to the SLCO2A1-related pathophysiology. The involvement of SLCO2A1 in the pathogenesis of ICNC may open exciting perceptions of this gene in nail development/morphogenesis.

P868 Clinical features of chronic enteropathy associated with SLCO2A1 gene

Abstract Background Chronic enteropathy associated with the SLCO2A1 gene (CEAS) is a hereditary disease caused by mutations of the SLCO2A1 gene which encodes a prostaglandin transporter. This disease is rare and intractable characterized by persistent blood and protein loss. There are few reports from Europe, and most reports are from Asian countries such as South Korea, China, and Japan. Because CEAS and Crohn's disease (CD) present ileal ulcers and stenoses, it is often difficult to distinguish CEAS from CD. Evaluation of characteristic upper gastrointestinal lesions observed in CEAS and extraintestinal findings, such as digital clubbing, periostosis, and pachydermia, can trigger suspicion of this disease, and genetic testing can be performed to confirm the diagnosis. Since little is known about the clinical features of CEAS, we conducted a nationwide survey in Japan. Methods All study participants provided written informed consent for genetic analysis. The present study was approved by the ethics committee of each institution. During the period between 2012 and 2022, 188 patients suspected of CEAS were enrolled in this study and checked to have SLCO2A1 gene mutations. We reviewed the clinical information of genetically confirmed CEAS patients. Results We confirmed the genetic analysis of 69 CEAS patients (24 males and 45 females) and found 19 different types of SLCO2A1 mutations. The median age at disease onset and diagnosis was 19 (range 1-69) and 42 (range 7-70) years, respectively. Parental consanguinity was present in 19 patients (26%). Although anaemia was present in almost all patients, only two patients experienced gross haematochezia. The median haemoglobin and serum total protein levels at diagnosis were 9.7 (range 2.3-14.4) and 5.3 (2.7-8.2) g/dl, respectively. Thirty-seven patients (54%) had undergone intestinal surgery. The most frequently involved gastrointestinal site was the ileum (94%), but the terminal ileum was rarely involved (4%). The lesions were shallow ulcers, varying in shape from circular, oblique, to longitudinal, sometimes forming pseudodiverticulum or luminal stenosis. The Gastric lesions were observed in 15 patients (22%) and duodenal lesions in 30 patients (43%). 20 patients (30%) had either mild digital clubbing, periostosis, or pachydermia. The extraintestinal findings, were more frequently found in males than in females (digital clubbing 52% vs 9%; periostosis 50% vs 10%; pachydermia 57% vs 0%). Conclusion Examination of the clinical features of CEAS reveals that ileal lesions are uniform and characteristic, but clinical features are diverse. Thirty per cent of patients with CEAS have extraintestinal features. There is a significant gender difference in extraintestinal features in CEAS patients.

A Complete Form of Pachydermoperiostosis Accompanied by a Pituitary Microadenoma

Pachydermoperiostosis is a rare genetic disease that is associated with HPGD (15-hydroxyprostaglandin dehydrogenase) and SLCO2A1 (solute carrier organic anion transporter family member 2A1) gene mutations. It is characterized by three major phenotypes, namely, pachydermia, periostosis, and digital clubbing. Clinically, misdiagnoses such as acromegaly and thyroid acropachy are commonly confused with pachydermoperiostosis. Integral medical history, physical examination, endocrinological tests, and multiple disciplinary cooperation are extremely significant in the accurate diagnosis of pachydermoperiostosis. The co-existence of pachydermoperiostosis and pituitary adenoma is rarely recorded and discussed. In this case, we present a young male patient with a complete form of pachydermoperiostosis and a nonfunctional pituitary microadenoma, which has rarely been reported.

Novel pathogenic variants in SLCO2A1 causing autosomal dominant primary hypertrophic osteoarthropathy

Primary hypertrophic osteoarthropathy (PHO), or pachydermoperiostosis, is characterized by a clinical association including digital clubbing, periostosis and pachydermia. SLCO2A1 and HPGD genes are both responsible for PHO. The pathology is classically defined as an autosomal recessive disorder with clinical variability ranging from a mild to more severe phenotype. However, the hypothesis for an autosomal dominant form suggested for a long time was only demonstrated for the first time in 2021 for SLCO2A1. We aimed to detect a second pathogenic variant by a deep sequencing of the entire SLCO2A1 and HPGD genes, associated with functional transcription analysis in PHO patients harboring only one heterozygous variant. Among 10 PHO patients, 4 presented a single pathogenic or probably pathogenic novel variant in SLCO2A1 in heterozygous status (NM_005630.3: c.234+1G > A, c.1523_1524delCT, c.1625G > A and c.31delC), and the others carried homozygous pathogenic variants. For heterozygous forms, we found no additional pathogenic variant in HPGD or SLCO2A1. PHO can be a dominant form with age at disease onset later than that for the recessive form. This dominant form is not exceptional in young adults. In conclusion, both modes of inheritance of PHO explain the clinical variability and the difference in age at disease onset. Molecular analysis is especially required in the incomplete form to distinguish it from secondary hypertrophic osteoarthropathy.

Functional analysis of mutant SLCO2A1 transporters found in patients with chronic enteropathy associated with SLCO2A1.

Chronic enteropathy associated with the solute carrier organic anion transporter family member 2A1 (SLCO2A1), or CEAS, causes anemia and hypoalbuminemia in young people. Dysfunction of the SLCO2A1 transporter protein is thought to involve genetic mutation, but mutant proteins have not been functionally characterized. We examined the prostaglandin E2 (PGE2 ) transport ability of recombinant SLCO2A1 proteins containing 11 SLCO2A1 mutations found in CEAS patients. Wild-type and mutant SLCO2A1 proteins were forcibly expressed in Xenopus laevis oocytes, and measurements of PGE2 uptake and transport capacity were compared. The membrane protein topology and functionality of the eight SLCO2A1 mutations involving single-nucleotide substitutions were predicted using computer analysis. The extent of functional disruption of the 11 SLCO2A1 mutations identified in CEAS patients was variable, with 10 mutations (421GT, 547GA, 664GA, 770GA, 830dupT, 830delT, 940+1GA, 1372GT, 1647GT, and 1807CT) resulting in loss or reduction of PGE2 transport, excluding 97GC. PGE2 transport ability of recombinant SLCO2A1 in X.laevis oocytes was hindered in 10/11 SLCO2A1 mutations identified in patients with CEAS. Further studies on the relationships between the different mutations and PGE2 transport and clinical features, such as severity, are needed.

Scalp "Petals" Sign in Touraine-Solente-Gole Syndrome.

HomeRadiologyVol. 305, No. 1 PreviousNext Reviews and CommentaryFree AccessImages in RadiologyScalp “Petals” Sign in Touraine-Solente-Gole SyndromeQiancheng Wang* , Lizhang Chen*Qiancheng Wang* , Lizhang Chen*Author AffiliationsFrom the Department of Neurology, North-Kuanren General Hospital, Chongqing, China (Q.W.); and Department of Neurology, West China Hospital, Sichuan University, Chengdu, China (L.C.).Address correspondence to Q.W. (email: [email protected]).Qiancheng Wang* Lizhang Chen*Published Online:Jun 21 2022https://doi.org/10.1148/radiol.213027MoreSectionsPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In * Q.W. and L.C. contributed equally to this work.An 18-year-old man presented with a 2-year history of progressive worsening of scalp folds. He also complained of recurring acne, hyperhidrosis, and seborrhea. A physical examination revealed pachydermia (thickening and wrinkling of the skin of the scalp and face), digital clubbing, and gynecomastia. Brain MRI scan showed scalp hypertrophy (Figure, A), which resembled petals. Radiography of both the legs showed periostitis (Figure, B). On the basis of these clinical and radiologic findings, Touraine-Solente-Gole syndrome was diagnosed. Genetic testing showed compound heterozygous mutations in the SLCO2A1 gene. Other secondary causes (eg, chronic hypoxia, inflammation, infections, or cancers) were excluded. After daily treatment with 200 mg of celecoxib, the patient’s acne and hyperhidrosis resolved.Images in an 18-year-old man who presented with a 2-year history of progressive worsening of scalp folds, recurrent acne, hyperhidrosis, and seborrhea consistent with Touraine-Solente-Gole syndrome. (A) Brain MRI scan obtained without contrast material shows scalp hypertrophy (scalp “petals” sign, arrow), and (B) left leg radiograph shows periostitis of the tibial and fibular shafts (arrows).Download as PowerPointOpen in Image Viewer Touraine-Solente-Gole syndrome is a rare hereditary disease that is characterized by pachydermia, periostosis, and digital clubbing (1). The radiologic scalp “petals” sign is consistent with clinical cutis verticis gyrata. The differential diagnosis of pachydermia includes cutis laxa, Ehlers-Danlos syndrome, Meretoja syndrome, Marfan syndrome, and pseudoxanthoma elasticum (2). Given the central role of prostaglandin E2 in the pathogenesis of Touraine-Solente-Gole syndrome, nonsteroidal anti-inflammatory drugs are often used as the first line of treatment.Disclosures of conflicts of interest: Q.W. No relevant relationships. L.C. No relevant relationships.* Q.W. and L.C. contributed equally to this work.

Cryptogenic multifocal ulcerating stenosing enteritis and other under-recognised small bowel inflammatory enteropathies.

Capsule endoscopy and more sensitive radiological techniques have resulted in more enteropathies being detected. A rare disease of unknown aetiology, 'cryptogenic multifocal ulcerating stenosing enteritis' or 'chronic nonspecific multiple ulcers of the small intestine' (CNSU), has long been recognised. This review aims to describe how disease can be better diagnosed and differentiated from other small bowel inflammatory disorders. Genetic studies have shown that some patients with CNSU (the term used in Japanese studies) express SLCO2A1 gene mutations, a gene which encodes a prostaglandin transporter expressed on vascular endothelium, allowing a more specific diagnosis of 'chronic enteropathy associated with SLCO2A1'. Mutations in the PLA2G4A gene result in cytosolic phospholipase A2α deficiency and reduced arachidonic acid for prostaglandin synthesis leading to a severe ulcerating, stenosing and fistulating small bowel disease. A 'prostaglandin-related enteropathy' should be considered in patients with atypical small bowel ulceration and stenosis. Genetic analysis will allow the detection of SLCO2A1 and PLA2G4A gene mutations. However, a careful history of medication use and a urinary metabolite screen may reveal the use of nonsteroidal anti-inflammatory drugs, a common cause of small bowel injury which is well recognised as being mediated by prostaglandin inhibition.

Chronic Enteropathy Associated with Solute Carrier Organic Anion Transporter Family, Member 2A1 (SLCO2A1) with Positive Immunohistochemistry for SLCO2A1 Protein.

Chronic enteropathy associated with solute carrier organic anion transporter family, member 2A1 (SLCO2A1) (CEAS) is a rare autosomal recessive hereditary disease characterized by chronic persistent anemia and hypoproteinemia. Its diagnosis typically requires a genetic analysis. The efficacy of immunohistochemical staining with SLCO2A1 polyclonal antibody as a pre-diagnostic tool for CEAS has been previously reported. We herein report a patient with CEAS in whom immunohistochemical staining confirmed SLCO2A1 protein expression. The immunopositive results may have been due to nonsense-mediated RNA decay. As immunohistochemical staining of SLCO2A1 protein may show immunopositive results, a genetic analysis should also be performed when CEAS is strongly clinically suspected.