SLCO2A1 Research Articles

Safety and efficacy of cyclooxygenase-2 inhibition for treatment of primary hypertrophic osteoarthropathy: A single-arm intervention trial

BackgroundPrimary hypertrophic osteoarthropathy (PHO) is a rare disease involving joint, bone and skin. Two underlying genes responsible for this disease—hydroxyprostaglandin dehydrogenase (HPGD) and solute carrier organic anion transporter family, member 2A1 (SLCO2A1)—are both associated with aberrant accumulation of prostaglandin E2 (PGE2). Cyclooxygenase-2 (COX-2) is a key enzyme in PGE2 synthesis. This study was intended to evaluate the safety and efficacy of COX-2 inhibitor in the treatment of PHO. MethodsWe recruited patients presenting to Peking Union Medical Hospital between January 2009 and December 2016 who were diagnosed with PHO. Participants were given the COX-2 inhibitor etoricoxib (60 mg once daily) and followed up for 9 months. Gene analysis was performed at baseline. The following data were collected at baseline and during treatment: visual analogue score (VAS), volume of the distal middle finger (VDMF), knee joint circumference (KJC), serum and urinary levels of prostaglandin E2 (PGE2) and PGE metabolite (PGE-M) and serum levels of inflammatory markers. ResultsA total of 27 patients were recruited, including seven patients with PHO type I (PHOAR1) carrying HPGD gene mutations and 20 patients with PHO type II (PHOAR2) carrying SLCO2A1 gene mutations. After treatment with etoricoxib, the majority of patients experienced resolution of symptoms including pachydermia (60.9%), joint swelling (100%), digital clubbing (74.1%) and hyperhidrosis (55.0%). In both the PHO subtypes, serum and urinary levels of PGE2 were elevated at baseline and declined sharply upon treatment. For PHOAR1 patients, serum and urinary PGE-M levels were relatively low and demonstrated minimal response to COX-2 inhibition. Among PHOAR2 patients, mean serum and urinary levels of PGE-M presented at a high level at baseline and were normalized after 3 months of treatment. No severe adverse effects were reported during the study period. ConclusionsWe found COX-2 inhibitor to be safe and effective for the treatment of PHO in our cohort. The translational potential of this articleThe underlying genes responsible for PHO suggest COX inhibitor as potential therapy, and our study demonstrates the efficacy and safety of this treatment.

A male Korean who was diagnosed with chronic enteropathy associated with SLCO2A1 (CEAS): case report with literature review

ObjectiveTo further disseminate the nomenclature of chronic enteropathy associated with SLCO2A1 (CEAS), especially for physicians in China and Korea where the genetic feature of SLCO2A1 gene mutations related hypertrophic osteoarthropathy...

Novel SLCO2A1 mutations cause gender differentiated pachydermoperiostosis.

Primary hypertrophic osteoarthropathy (PHO) is a rare familial disorder with reduced penetrance for females. The genetic mutations associated with PHO have been identified in HPGD and SLCO2A1, which involved in prostaglandin E2 metabolism. Here, we report 5 PHO patients from four non-consanguineous families. Two heterozygous mutations in solute carrier organic anion transporter family member 2A1 (SLCO2A1) were identified in two brothers by whole-exome sequencing. Three heterozygous mutations and one homozygous mutation were identified in other three PHO families by Sanger sequencing. However, there was no mutation in HPGD. These findings confirmed that homozygous or compound heterozygous mutations of SLCO2A1 were the pathogenic cause of PHO. A female individual shared the same mutations in SLCO2A1 with her PHO brother but did not have any typical PHO symptoms. The influence of sex hormones on the pathogenesis of PHO and its implication were discussed.

Genetic analysis is helpful for the diagnosis of small bowel ulceration.

The widespread use of capsule endoscopy and balloon-assisted endoscopy has provided easy access for detailed mucosal assessment of the small intestine. However, the diagnosis of rare small bowel diseases, such as cryptogenic multifocal ulcerous stenosing enteritis (CMUSE), remains difficult because clinical and morphological features of these diseases are obscure even for gastroenterologists. In an issue of this journal in 2017, Hwang et al reviewed and summarized clinical and radiographic features of 20 patients with an established diagnosis of CMUSE. Recently, recessive mutations in the PLA2G4A and SLCO2A1 genes have been shown to cause small intestinal diseases. The small bowel ulcers in each disease mimic those in the other and furthermore those found in nonsteroidal anti-inflammatory drug-induced enteropathy. These recent and novel findings suggest that a clinical diagnosis exclusively based on the characteristics of small bowel lesions is possibly imprecise. Genetic analyses seem to be inevitable for the diagnosis of rare small bowel disorders such as CMUSE.

P129 USEFULNESS OF PROSTAGLANDIN E-MAJOR URINARY METABOLITE MEASUREMENT FOR THE DIFFERENTIATION BETWEEN CHRONIC ENTEROPATHY ASSOCIATED WITH SLCO2A1 GENE (CEAS) AND CROHN’S DISEASE

Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a rare intractable disease characterized by persistent anemia and hypoproteinemia due to multiple small intestinal ulcers. Recently, we identified that the disease is caused by loss-of-function mutations of SLCO2A1 gene, encoding a prostaglandin transporter. Because clinical features of CEAS mimic those of Crohn’s disease (CD) with respect to intestinal ulcers and stenosis, a convenient screening test other than genetic analysis is required. Our preliminary study demonstrated higher urinary levels of prostaglandin metabolites in patients with CEAS than in healthy controls. In this study, we investigated the usefulness of prostaglandin E-major urinary metabolites (PGE-MUM) to discriminate CEAS from CD. Seventeen Japanese patients with CEAS and 97 CD patients were recruited. The diagnosis of CEAS was based on the published clinical criteria and genetic analysis. Urine samples were collected, and PGE-MUM concentration was measured by radioimmunoassay. Logistic regression analysis was used to calculate the odds ratio (OR). We used ROC analysis to determinate the optimal cut-off value of PGE-MUM. PGE-MUM concentration was significantly higher in CEAS group than in CD group (median 121 vs 21.7 μg/g×Cre, p < 0.0001). Crude OR of 1 log unit change for the PGE-MUM for the differentiation between CEAS and CD was calculated to be 7.46 (95% confidence interval [CI] 3.14–17.7). This association was also significant after adjusting confounding factors including age, gender, history of pulmonary disease, surgical history, and CRP (adjusted OR 21.1, 95%CI 4.72–94.4). The optimal cut-off value of PGE-MUM was determined to be 50.9 μg/g×Cre, which identified CEAS with 93.7% sensitivity and 80.4% specificity (area under the ROC curve 0.905). The measurement of PGE-MUM is considered to be a useful and convenient test for discriminating CEAS from CD.

Clinical features of chronic enteropathy associated with SLCO2A1 gene: a new entity clinically distinct from Crohn\u2019s disease

BackgroundChronic enteropathy associated with SLCO2A1 gene (CEAS) is a hereditary disease caused by mutations in the SLCO2A1 gene and characterized by multiple small intestinal ulcers of nonspecific histology. SLCO2A1 is also a causal gene of primary hypertrophic osteoarthropathy (PHO). However, little is known about the clinical features of CEAS or PHO.MethodsSixty-five Japanese patients recruited by a nationwide survey of CEAS during 2012–2016 were enrolled in this present study. We reviewed the clinical information of the genetically confirmed CEAS patients.ResultsWe identified recessive SLCO2A1 mutations at 11 sites in 46 patients. Among the 46 patients genetically confirmed as CEAS, 13 were men and 33 were women. The median age at disease onset was 16.5 years, and parental consanguinity was present in 13 patients (28%). Anemia was present in 45 patients (98%), while a single patient experienced gross hematochezia. All patients showed relatively low inflammatory markers in blood tests (median CRP 0.20 mg/dl). The most frequently involved gastrointestinal site was the ileum (98%), although no patient had mucosal injuries in the terminal ileum. Mild digital clubbing or periostosis was found in 13 patients (28%), with five male patients fulfilling the major diagnostic criteria of PHO.ConclusionsThe clinical features of CEAS are distinct from those of Crohn’s disease. Genetic analysis of the SLCO2A1 gene is therefore recommended in patients clinically suspected of having CEAS.

Pachydermoperiostosis: a case report

Pachydermoperiostosis (PHO) or primary hypertrophic osteoarthropathy is a rare genetic disease that typically begins during childhood or adolescence. It is characterized by digital clubbing, pachydermia and periosteal reaction and progresses gradually over the years prior to disease stabilization. Two genes are reported to be associated with PHO – HPGD and SLCO2A1. These genes are involved in prostaglandin E2 metabolism.&#x0D; We present a description of a 19-year-old patient with PHO. We found two mutations in the SLCO2A1 gene: p.Gly183Ar (chr3:133673888, NM_005630.2:c.547G&gt;A) and p.Cys444Gly (chr3:133664070, NM_005630.2:c.1330T&gt;G) through molecular genetic analysis. The mutation (p.Cys444Gly) has never been recorded in previous studies.&#x0D; This work expands our knowledge of the mutation spectrum of PHO, which will facilitate faster genetic diagnosis and interpretation of genetic information in prenatal diagnosis and genetic counseling.

Roles of Organic Anion Transporting Polypeptide 2A1 (OATP2A1/SLCO2A1) in Regulating the Pathophysiological Actions of Prostaglandins.

Solute carrier organic anion transporter family member 2A1 (OATP2A1, encoded by the SLCO2A1 gene), which was initially identified as prostaglandin transporter (PGT), is expressed ubiquitously in tissues and mediates the distribution of prostanoids, such as PGE2, PGF2α, PGD2 and TxB2. It is well known to play a key role in the metabolic clearance of prostaglandins, which are taken up into the cell by OATP2A1 and then oxidatively inactivated by 15-ketoprostaglandin dehydrogenase (encoded by HPGD); indeed, OATP2A1-mediated uptake is the rate-limiting step of PGE2 catabolism. Consequently, since OATP2A1 activity is required for termination of prostaglandin signaling via prostanoid receptors, its inhibition can enhance such signaling. On the other hand, OATP2A1 can also function as an organic anion exchanger, mediating efflux of prostaglandins in exchange for import of anions such as lactate, and in this context, it plays a role in the release of newly synthesized prostaglandins from cells. These different functions likely operate in different compartments within the cell. OATP2A1 is reported to function at cytoplasmic vesicle/organelle membranes. As a regulator of the levels of physiologically active prostaglandins, OATP2A1 is implicated in diverse physiological and pathophysiological processes in many organs. Recently, whole exome analysis has revealed that recessive mutations in SLCO2A1 cause refractory diseases in humans, including primary hypertrophic osteoarthropathy (PHO) and chronic non-specific ulcers in small intestine (CNSU). Here, we review and summarize recent information on the molecular functions of OATP2A1 and on its physiological and pathological significance.

Identification of mutations in the prostaglandin transporter gene SLCO2A1 and phenotypic comparison between two subtypes of primary hypertrophic osteoarthropathy (PHO): A single-center study

Primary hypertrophic osteoarthropathy (PHO) is an inherited disease characterized by digital clubbing, periostosis, and pachydermia. Based on two causative genes, hydroxyprostaglandin dehydrogenase (HPGD) and solute carrier organic anion transporter family member 2A1 (SLCO2A1), PHO is categorized into two subtypes: hypertrophic osteoarthropathy, primary, autosomal recessive 1 (PHOAR1) and hypertrophic osteoarthropathy, primary, autosomal recessive 2 (PHOAR2). In this study, we summarized the clinical manifestations and analyzed SLCO2A1 gene in 23 PHOAR2 patients in our center. As a result, 18 patients displayed complete phenotypes of PHO with digital clubbing, periostosis, and pachydermia. 29 mutations were found in total, and 22 of them were novel mutations including 13 missense, three nonsense, four deletion, one frame-shift and one splicing site mutations. Compared with nine PHOAR1 patients we previously reported, PHO patients with SLCO2A1 mutations were all male and presented with a later onset age. Peptic ulcers and myelofibrosis occurred only in PHOAR2 patients. The urinary level of prostaglandin E2 metabolite (PGEM) is significantly higher in PHOAR2 patients than that in PHOAR1 group. In conclusion, this study was the largest cohort to date to summarize PHOAR2 patients and to assess the phenotypic difference between two subtypes of PHO. The difference of urinary PGEM concentration between two subtypes is helpful for the differential diagnosis of PHO.

Pachydermoperiostosis: The value of molecular diagnosis

Pachydermoperiostosis is a rare autosomal recessive genetic disorder characterized by the association of periostosis and pachydermia. To date, two genes involved in prostaglandin metabolism, HPGD and SLCO2A1, have been identified. A 7-year-old girl presented digital clubbing of the hands and feet, curved nails, hyperhidrosis, and pachydermia, as well as eczema of the trunk and limbs. The diagnosis of pachydermoperiostosis was confirmed by the detection of a homozygous mutation in the HPGD gene. The second case concerned a 41-year-old male with acral and cephalic pachydermia (cutis verticis gyrata), and palmoplantar keratoderma. Bone X-rays showed changes in the distal ends of several bones. The diagnosis of pachydermoperiostosis was confirmed by the detection of a homozygous mutation in the SLCO2A1 gene. The genotype/phenotype correlation suggests that patients with SLCO2A1 mutations will develop the symptoms later in life, but that these will be more severe, with a greater likelihood of cutis verticis gyrata and joint involvement compared with patients presenting HPGD mutations. In addition, hereditary enteropathy has recently been described in patients with SLCO2A1 mutations, which could account for the gastrointestinal picture seen in the second patient. Finally, on account of cases involving myelofibrosis associated with mutations in the SLCO2A gene, these patients should have a hematologic follow-up. Given the genotype/phenotype correlations illustrated by these cases, it would appear useful to propose molecular diagnosis for patients presenting pachydermoperiostosis.

Pachydermoperiostosis of the complete type: A novel missense mutation c.101T > C in the SLCO2A1 gene

We report on a rare case of pachydermoperiostosis (PDP) in a 25-year-old male who was admitted to our hospital because of enlargement of fingers and toes. Through examination, we found some typical features on the patient including finger clubbing, periostosis, pachydermia, and cutis verticis gyrata (CVG). But laboratory tests were almost within normal ranges, which ruled out rheumatic arthritis, osteopulmonary arthropathy, thyroid acropathy, and acromegaly. Then, we diagnosed this case as PDP, which was confirmed by gene sequencing. The pathogenesis is concerned with abnormal rise of the level of PGE2 that results from the solute carrier organic anion transporter family member 2A1 (SLCO2A1) gene defect. Meanwhile, we found a novel missense mutation c.101T > C of the SLCO2A1 gene in the patient with PDP.

Chronic Enteropathy Associated With SLCO2A1 Gene [CEAS]-Characterisation of an Enteric Disorder to be Considered in the Differential Diagnosis of Crohn's Disease.

Small intestinal ulcers include mucosal damage caused by drugs, particularly nonsteroidal anti-inflammatory drugs [NSAIDs], infectious diseases, and idiopathic inflammatory bowel disease. Previously, a group of Japanese investigators reported an unusual and uncommon type of enteritis and referred to the condition as chronic nonspecific multiple ulcers of the small intestine [CNSU]. CNSU is characterised by chronic blood and protein loss through persistent small intestinal ulcers. Recently, four candidate mutations in the solute carrier organic anion transporter family, member 2A1 [SLCO2A1] gene, encoding a prostaglandin transporter, were identified by whole-exome sequencing in patients with CNSU. However, because the name 'CNSU' was somewhat ambiguous, the more appropriate nomenclature of 'chronic enteropathy associated with the SLCO2A1 gene' [CEAS] has been suggested. CEAS ulcers are characterised by multiple, circular or eccentric oblique, shallow lesions with discrete margins. The most frequently affected site of CEAS is the ileum, in contrast to 'cryptogenic multifocal ulcerous stenosing enteritis [CMUSE]', for which the most frequent site is the jejunum. Impaired prostaglandin utilisation is thought to cause the small intestinal mucosal damage observed in CEAS, CMUSE, and NSAID-induced enteropathy. This review article focuses on endoscopic and clinical features of genetically diagnosed CEAS, accumulated in a nationwide survey, and illustrates the observations in the format of an atlas.

Primary hypertrophic osteoarthropathy due to a novel SLCO2A1 mutation masquerading as acromegaly

SummaryA 20-year-old man with an 8-year history of progressive enlargement of his hands and feet, coarsening facial features, painful joints and thickened, oily skin was referred for investigation of acromegaly. On examination, the subject was of normal height and weight. He had markedly increased skin thickness around the forehead, eyelids and scalp with redundant skin folds. Bilateral painful knee swelling was accompanied by enlargement of the extremities, and his fingers were markedly clubbed. Routine hematological, biochemical and hormonal blood tests, including GH and IGF-1 were normal. The clinical picture suggested primary hypertrophic osteoarthropathy (PHOA) rather than acromegaly and radiological studies were supportive of this, demonstrating increased subperiosteal bone formation and increased bone density and cortical thickening. There was widespread joint disease, with narrowing of joint spaces, whereas the knees demonstrated effusions and calcification. A skull X-ray revealed calvarial hyperostosis and a normal sellar outline. Family history was negative. Genetic studies were performed on peripheral blood leukocyte DNA for mutations in the two genes associated with PHOA, 15-hydroxyprostaglandin dehydrogenase (HPGD; OMIM: 601688) and solute carrier organic anion transporter family member 2A1 (SLCO2A1; OMIM: 601460). The sequence of HPGD was normal, whereas the subject was homozygous for a novel pathological variant in SLCO2A1, c.830delT, that predicted a frameshift and early protein truncation (p.Phe277Serfs*8). PHOA, also known as pachydermoperiostosis, is a rare entity caused by abnormal prostaglandin E2 metabolism, and both HPGD and SLCO2A1 are necessary for normal prostaglandin E2 handling. High prostaglandin levels lead to bone formation and resorption and connective tissue inflammation causing arthropathy, in addition to soft tissue swelling.Learning points:The differential diagnosis of enlarged extremities, coarsened facial features, skin changes and increased sweating in suspected acromegaly is quite limited and primary hypertrophic osteoarthropathy (PHOA) is one of the few conditions that can mimic acromegaly at presentation.PHOA is not associated with abnormalities in GH and IGF-1 secretion and can be readily differentiated from acromegaly by hormonal testing.Clubbing in the setting of diffuse enlargement of joints and extremities in addition to skin changes should alert the physician to the possibility of PHOA, as clubbing is not a usual feature of acromegaly. Underlying causes of secondary hypertrophic osteoarthroapthy (e.g. bronchial neoplasia) should be considered.PHOA is a very rare condition caused by abnormalities in prostaglandin metabolism and has two known genetic causes (HPGD and SLCO2A1 mutations). SLCO2A1 gene mutations lead usually to autosomal recessive PHOA; fewer than 50 SLCO2A1 mutations have been described to date and the current case is only the second in a Hispanic patient.Treatment of primary hypertrophic osteoarthropathy is focused on the management of joint pain usually in the form of non-steroidal anti-inflammatory drug therapy.

Pediatric-onset Chronic Nonspecific Multiple Ulcers of Small Intestine: A Nationwide Survey and Genetic Study in Japan.

We performed a Japanese nationwide survey of pediatric-onset chronic nonspecific multiple ulcers of the small intestine between January 2000 and July 2013 in 176 institutions of pediatric surgery or pediatric gastroenterology and clarified the clinical features associated with genetic abnormalities in the Solute Carrier Organic Anion Transporter Family, Member 2A1 (SLCO2A1) gene. A total of 4 cases (3 girls and 1 boy) were diagnosed in this series, which had to be differentiated from Crohn disease, Behçet disease, tuberculosis, or drug-induced enteropathy. Clinical symptoms appeared in infants and accurate diagnosis required several years. Medical therapies for inflammatory bowel disease were administered in all patients; however, 2 of the 4 patients had mutation in the SLCO2A1 gene which are responsible for primary hypertrophic osteoarthopathy, and underwent strictureplasty or ileal resection after long-term follow-up. Pediatric gastroenterologists should include this new entity in the differential diagnosis of small intestinal ulcers and inflammatory bowel disease.

P215 Clinical features of chronic enteropathy associated with SLCO2A1 gene (CEAS)

Background: Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a rare hereditary disease caused by mutations in SLCO2A1 gene, encoding a prostaglandin transporter. CEAS resembles Crohn's disease (CD) in presenting multiple small intestinal ulcers. However, because immunosuppressive therapies such as corticosteroid and anti-tumor necrosis factor-alpha antibody therapies are ineffective for CEAS in contrast to CD, recognition and precise diagnosis of CEAS are critical to avoid unnecessary therapies. Methods: Forty-one Japanese patients (10 male and 31 female) were diagnosed with CEAS by clinical findings and genetic analysis during a period of 2012 to 2016 and they were enrolled in this study. To identify the clinical features of CEAS, we reviewed the clinical information for the patients. In addition, because SLCO2A1 gene has also been reported as a causative gene of primary hypertrophic osteoarthropathy (PHO; OMIM 614441), we investigated whether CEAS patients had clinical manifestations of PHO. Results: We found recessive SLCO2A1 mutations located at 11 sites. Among the identified SLCO2A1 mutations, a splice-site mutation of intron 7 (c.940+1G>A) was the most frequent, and 17 of the 41 patients were homozygous for this mutation (41%). Median age at onset was 17 (1 to 69) and parental consanguinity was present in 12 patients (29%). Anemia and abdominal pain were present in 40 (98%) and 16 (39%) patients, respectively. On the other hand, there were little inflammatory findings in blood tests (median CRP 0.16mg/dl). During the course of the disease, 27 patients (66%) had undergone one or more surgeries such as partial resection of the small intestine. The most frequently involved gastrointestinal site was ileum (98%), but there was no patient with ulcerations in the terminal ileum. The stomach and duodenum were affected in 11 (27%) and 18 (44%) patients, respectively. Although no patients had clinical manifestations of PHO that required treatment, mild digital clubbing or periostosis was present in 12 patients (29%). Moreover, 4 male patients fulfilled the major clinical criteria for PHO, having digital clubbing, periostosis, and pachydermia. Conclusions: Although CEAS mimics CD, some clinical features of CEAS are different from those of CD, such as low inflammatory findings, terminal ileum-sparing ulcerations and extraintestinal manifestations. Genetic analysis should be considered if CEAS is clinically suspected.

Expression and regulation of prostaglandin transporters, ATP-binding cassette, subfamily C, member 1 and 9, and solute carrier organic anion transporter family, member 2A1 and 5A1 in the uterine endometrium during the estrous cycle and pregnancy in pigs.

ObjectiveProstaglandins (PGs) function in various reproductive processes, including luteolysis, maternal pregnancy recognition, conceptus development, and parturition. Our earlier study has shown that PG transporters ATP-binding cassette, subfamily C, member 4 (ABCC4) and solute carrier organic anion transporter family, member 2A1 (SLCO2A1) are expressed in the uterine endometrium in pigs. Since several other PG transporters such as ABCC1, ABCC9, SLCO4C1, and SLCO5A1 are known to be present in the uterine endometrium, this study investigated the expression of these PG transporters in the porcine uterine endometrium and placenta.MethodsUterine endometrial tissues were obtained from gilts on day (D) 12 and D15 of the estrous cycle and days 12, 15, 30, 60, 90, and 114 of pregnancy.ResultsABCC1, ABCC9, SLCO4C1, and SLCO5A1 mRNAs were expressed in the uterine endometrium, and levels of expression changed during the estrous cycle and pregnancy. Expression of ABCC1 and ABCC9 mRNAs was localized mainly to luminal and glandular epithelial cells in the uterine endometrium, and chorionic epithelial cells during pregnancy. Conceptuses during early pregnancy and chorioallantoic tissues from mid to late pregnancy also expressed these PG transporters. Estradiol-17β increased the expression of ABCC1 and SLCO5A1, but not ABCC9 and SLCO4C1 mRNAs and increasing doses of interleukin-1β induced the expression of ABCC9, SLCO4C1, and SLCO5A1 mRNAs in endometrial explant tissues.ConclusionThese data showed that several PG transporters such as ABCC1, ABCC9, SLCO4C1, and SLCO5A1 were expressed at the maternal-conceptus interface, suggesting that these PG transporters may play an important role in the establishment and maintenance of pregnancy by regulating PG transport in the uterine endometrium and placenta in pigs.

Chronic nonspecific multiple ulcers of the small intestine (CNSU) and chronic enteropathy associated with SLCO2A1 (CEAS).

Chronic nonspecific multiple ulcers of the small intestine (CNSU) and chronic enteropathy associated with SLCO2A1 (CEAS).

A case of pachydermoperiostosis with c.940+1G > A and c.1279_1290del12 in the SLCO2A1 gene

A case of pachydermoperiostosis with c.940+1G > A and c.1279_1290del12 in the SLCO2A1 gene

A case of pachydermoperiostosis caused by a deletion mutation in the HPGD gene

Objective To confirm a case of pachydermoperiostosis (primary hypertrophic osteoarthropathy) at the molecular level by gene sequencing. Methods Peripheral blood samples were obtained from a 26-year-old male patient with pachydermoperiostosis and his parents, and DNA was extracted from these blood samples. Polymerase chain reaction (PCR) was performed to amplify all the exons of HPGD and SLCO2A1 genes, and gene sequencing to identify gene mutations. According to sequencing results, the spatial structure of relevant proteins was predicted. Results Gene sequencing showed a homozygous frame-shifting mutation c.310_311delCT (p.L104AfsX3) in exon 3 of the HPGD gene in the patient. His mother was a heterozygous carrier of the mutation, but no mutation was identified in his father. The prediction of spacial structure of proteins revealed that the above gene mutation could shorten the length of the encoded peptide by about 60%. Conclusion Typical clinical manifestations and imaging findings are helpful for the primary diagnosis of pachydermoperiostosis, while mutation analysis of HPGD and SLCO2A1 genes is a main approach to its final diagnosis. Key words: Osteoarthropathy, primary hypertrophic; Mutation; HPGD gene; SLCO2A1 gene

A Novel Heterozygous Mutation in the SLCO2A1 Gene in Family with Primary Hypertrophic Osteoarthropathy

A Novel Heterozygous Mutation in the SLCO2A1 Gene in Family with Primary Hypertrophic Osteoarthropathy