Chronic Enteropathy Associated with &lt;i&gt;SLCO2A1&lt;/i&gt; with Pachydermoperiostosis

Tsuzuki, Yoshikazu; Aoyagi, Ryutaro; Miyaguchi, Kazuya; Ashitani, Keigo; Ohgo, Hideki; Yamaoka, Minoru; Ishizawa, Keisuke; Kayano, Hidekazu; Hisamatsu, Tadakazu; Umeno, Junji; Hosoe, Naoki; Matsumoto, Takayuki; Nakamoto, Hidetomo; Imaeda, Hiroyuki

doi:10.2169/internalmedicine.4756-20

Cited by 9 publications

(6 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Так, у пациентки Х. на фоне бесконтрольного применения неселективных НПВС манифестировали острые язвы желудка. Гастрои энтеропатии при пахидермопериостозе встречаются, однако в большей степени характерны для пациентов с мутацией в гене SLCO2A1 [7,19,20]. Согласно недавнему исследованию, у пациентов женского пола с аутосомно-рецессивной мутацией в гене SLCO2A1 хроническая энтеропатия может развиваться изолированно, без сопутствующей клинической картины пахидермопериостоза [19].…”

Section: Discussionunclassified

Features of the clinical course of pachydermoperiostosis with a verified mutation in the European type gene

Frolova,

Golounina,

Mamedova

et al. 2023

Osteopor Bone Dis

View full text Add to dashboard Cite

Pachydermoperiostosis (primary hypertrophic osteoarthropathy) is an orphan disease, the main clinical manifestations of which include pin-shaped deformity of the fingers according to the type of «drumsticks», periostosis (non-inflammatory changes of the periosteum) of tubular bones, pachydermia of the face (hypertrophy and hyperplasia of all skin layers). Two genes associated with the development of pachydermoperiostosis are known — HPGD and SLCO2A1. Mutations in these genes lead to impaired prostaglandin E2 metabolism. This article describes a clinical case of a patient with pachydermoperiostosis, in which two mutations in the HPGD gene were detected during a molecular genetic study: in 1 exon (chr4-174522451-T-A, NM_000860.6:c.1A>T) and in 2 exon (chr4-174521985-AG-, NM_000860.6:c.175_176del) in compound-heterozygous state, while the c.1A>T mutation was previously described once, and the revealed biallelic combination of mutations in the HPGD gene was not previously found in the literature. This clinical case of pachydermoperiostosis is the second described in the Russian population, and the first with confirmed mutations in the HPGD gene. The article expands the knowledge about the correlation of genotype and phenotype in pachydermoperiostosis, which contributes to a faster and more correct interpretation of genetic information during genetic counseling.

show abstract

Section: Discussionunclassified

Features of the clinical course of pachydermoperiostosis with a verified mutation in the European type gene

Frolova,

Golounina,

Mamedova

et al. 2023

Osteopor Bone Dis

View full text Add to dashboard Cite

show abstract

“…24,25 Indeed, patients with CEAS coexisting with PDP have been reported. 26,27 Umeno et al reported that mild digital clubbing or periostosis was found in 13 of 46 CEAS patients (28%), with five male patients fulfilling the major diagnostic criteria of PDP. 23 The relationships between clinical characteristics of CEAS including SLCO2A1 gene variation and coexistence of PDP have not yet been clarified.…”

Section: Discussionmentioning

confidence: 99%

“…PDP is an intractable disease of skin and periosteum with three main symptoms: periosteal bone thickening, mainly digital clubbing and proliferation of the long canal bones; skin hypertrophic changes including cutis verticis gyrata and skin symptoms such as seborrhea and acne; and joint pain 24,25 . Indeed, patients with CEAS coexisting with PDP have been reported 26,27 . Umeno et al .…”

Section: Discussionmentioning

confidence: 99%

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

Seki

Tanaka

Kimura

et al. 2022

J of Gastro and Hepatol

Self Cite

View full text Add to dashboard Cite

Background and Aim 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. Methods 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. Results 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. Conclusion 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.

show abstract

“…Mutations (missense, nonsense, deletions, and frame shifts) are spread throughout the gene and were found in each of the 12 transmembrane helices, as well as in the exra-and intracellular loops, and even at the start codon (see Table 4 and Figure 4 in [155]). Although there were differences in age of onset and occurrence in males and females, clinical manifestations characteristic of PHO, such as pachydermia (abnormal thickening of the facial and head skin), periostosis (abnormal formation of periosteal bone), and finger clubbing, were found together with features of CEAS, such as chronic bleeding with multiple small-intestinal ulcers [156][157][158][159]. Mutations, such as G222R, G255E, and P219L, were suggested to affect the transport function of SLCO2A1 protein based on protein modelling [116,117].…”

Section: Physiological/pathophysiological Implications Of Maxi-clmentioning

confidence: 99%

The ATP-Releasing Maxi-Cl Channel: Its Identity, Molecular Partners, and Physiological/Pathophysiological Implications

Sabirov

Islam

Okada

et al. 2021

Life

View full text Add to dashboard Cite

The Maxi-Cl phenotype accounts for the majority (app. 60%) of reports on the large-conductance maxi-anion channels (MACs) and has been detected in almost every type of cell, including placenta, endothelium, lymphocyte, cardiac myocyte, neuron, and glial cells, and in cells originating from humans to frogs. A unitary conductance of 300–400 pS, linear current-to-voltage relationship, relatively high anion-to-cation selectivity, bell-shaped voltage dependency, and sensitivity to extracellular gadolinium are biophysical and pharmacological hallmarks of the Maxi-Cl channel. Its identification as a complex with SLCO2A1 as a core pore-forming component and two auxiliary regulatory proteins, annexin A2 and S100A10 (p11), explains the activation mechanism as Tyr23 dephosphorylation at ANXA2 in parallel with calcium binding at S100A10. In the resting state, SLCO2A1 functions as a prostaglandin transporter whereas upon activation it turns to an anion channel. As an efficient pathway for chloride, Maxi-Cl is implicated in a number of physiologically and pathophysiologically important processes, such as cell volume regulation, fluid secretion, apoptosis, and charge transfer. Maxi-Cl is permeable for ATP and other small signaling molecules serving as an electrogenic pathway in cell-to-cell signal transduction. Mutations at the SLCO2A1 gene cause inherited bone and gut pathologies and malignancies, signifying the Maxi-Cl channel as a perspective pharmacological target.

show abstract

Chronic Enteropathy Associated with <i>SLCO2A1</i> with Pachydermoperiostosis

Cited by 9 publications

References 14 publications

Features of the clinical course of pachydermoperiostosis with a verified mutation in the European type gene

Features of the clinical course of pachydermoperiostosis with a verified mutation in the European type gene

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

The ATP-Releasing Maxi-Cl Channel: Its Identity, Molecular Partners, and Physiological/Pathophysiological Implications

Contact Info

Product

Resources

About