{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T20:48:32Z","timestamp":1788382112672,"version":"build-2803163510"},"reference-count":37,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Symptoms of pudendal nerve neuropathy may overlap with various symptoms of interstitial cystitis (IC). As documented, there is a well-established correlation between the genes involved in ATP metabolism, neuropathy, and IC. ATP-binding cassette (ABC) transporters genes, in fact, are vital for ATP signaling. This study aims to associate the ABCF2 gene with a suspected pudendal nerve neuropathy and IC. Methods: Histological analysis was conducted for diagnosing IC while the genetic variant was identified by whole exome sequencing (WES) Trio and confirmed through Sanger. Results: We report a patient with IC, confirmed by histological examination, presenting with a suspected bladder and pudendal nerve neuropathy, though not analytically confirmed. Histological analysis revealed urothelial detachment caused by a dense subepithelial lymphocytic infiltrate, predominantly composed of mast cells, which serve as key diagnostic markers for interstitial cystitis (IC). WES analysis identified the heterozygous genetic variant c.1253T&gt;G p.Phe418Cys within ABCF2 gene, precisely in its functional domain which actively operates in the hydrolysis of ATP energizing various biological systems. As reported, this gene displays high expression patterns in bladder tissue. The variant, absent in the healthy brother, was inherited from the father which presents mosaicism. The in silico prediction analyses classified this variant as pathogenic, identifying potential alterations in the protein structure. Conclusions: Although the precise role of ABCF2 should be supported by further studies, we hypothesize that its disruption might impair ATP metabolism, likely altering the nociceptive response and leading to the patient\u2019s neuropathy. Further analyses are imperative to validate this research, for laying the groundwork for a specific therapy targeting the genetic dysregulation involved in this condition.<\/jats:p>","DOI":"10.3390\/genes16030281","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T08:28:31Z","timestamp":1740558511000},"page":"281","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Potential Role of ABCF2 Gene in Pudendal Nerve Neuropathy and Interstitial Cystitis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8999-3365","authenticated-orcid":false,"given":"Antonino","family":"Musumeci","sequence":"first","affiliation":[{"name":"Oasi Research Institute-IRCCS, 94018 Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3026-8510","authenticated-orcid":false,"given":"Mirella","family":"Vinci","sequence":"additional","affiliation":[{"name":"Oasi Research Institute-IRCCS, 94018 Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5631-9991","authenticated-orcid":false,"given":"Simone","family":"Treccarichi","sequence":"additional","affiliation":[{"name":"Oasi Research Institute-IRCCS, 94018 Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7399-964X","authenticated-orcid":false,"given":"Alda","family":"Ragalmuto","sequence":"additional","affiliation":[{"name":"Oasi Research Institute-IRCCS, 94018 Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Bruno","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences and Advanced Technologies \u201cG.F. Ingrassia\u201d, Anatomic Pathology, University of Catania, 95131 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2680-1804","authenticated-orcid":false,"given":"Giordana","family":"Tinniriello","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences and Advanced Technologies \u201cG.F. Ingrassia\u201d, Anatomic Pathology, University of Catania, 95131 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5101-7836","authenticated-orcid":false,"given":"Jessica","family":"Farina","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences and Advanced Technologies \u201cG.F. Ingrassia\u201d, Anatomic Pathology, University of Catania, 95131 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concetta","family":"Federico","sequence":"additional","affiliation":[{"name":"Department Biological, Geological and Environmental Sciences, University of Catania, Via Androne 81, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7568-5823","authenticated-orcid":false,"given":"Salvatore","family":"Saccone","sequence":"additional","affiliation":[{"name":"Department Biological, Geological and Environmental Sciences, University of Catania, Via Androne 81, 95124 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8667-8223","authenticated-orcid":false,"given":"Francesco","family":"Cal\u00ec","sequence":"additional","affiliation":[{"name":"Oasi Research Institute-IRCCS, 94018 Troina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Porru","sequence":"additional","affiliation":[{"name":"Urology Department, Fondazione IRCCS, San Matteo Hospital, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"E449","DOI":"10.36076\/ppj\/2019.19.E449","article-title":"Pudendal Neuralgia Due to Pudendal Nerve Entrapment: Warning Signs Observed in Two Cases and Review of the Literature","volume":"19","author":"Ploteau","year":"2016","journal-title":"Pain Physician"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1097\/JU.0000000000002756","article-title":"Diagnosis and Treatment of Interstitial Cystitis\/Bladder Pain Syndrome","volume":"208","author":"Clemens","year":"2022","journal-title":"J. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1159\/000115400","article-title":"Role of Pudendal Canal Syndrome in the Pathogenesis of Interstitial Cystitis and Its Treatment by Pudendal Canal Decompression","volume":"2","author":"Shafik","year":"2008","journal-title":"Curr. Urol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/iju.12379","article-title":"Gynecological Disorders in Bladder Pain Syndrome\/Interstitial Cystitis Patients","volume":"21","author":"Cervigni","year":"2014","journal-title":"Int. J. Urol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"bcr2015213513","DOI":"10.1136\/bcr-2015-213513","article-title":"Combined Site-Specific Sacral Neuromodulation and Pudendal Nerve Release Surgery in a Patient with Interstitial Cystitis and Persistent Arousal","volume":"2016","author":"Armstrong","year":"2016","journal-title":"BMJ Case Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1111\/iju.14229","article-title":"Interstitial Cystitis\/Bladder Pain Syndrome: The Evolving Landscape, Animal Models and Future Perspectives","volume":"27","author":"Akiyama","year":"2020","journal-title":"Int. J. Urol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2394","DOI":"10.1002\/nau.24500","article-title":"Presenting an Atlas of Hunner Lesions in Interstitial Cystitis Which Can Be Identified with Office Cystoscopy","volume":"39","author":"Ronstrom","year":"2020","journal-title":"Neurourol. Urodyn."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Padilla-Fern\u00e1ndez, B., Hern\u00e1ndez-Hern\u00e1ndez, D., and Castro-D\u00edaz, D.M. (2022). Current Role of Neuromodulation in Bladder Pain Syndrome\/Interstitial Cystitis. Ther. Adv. Urol., 14.","DOI":"10.1177\/17562872221135941"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e38","DOI":"10.14440\/bladder.2019.789","article-title":"Purinergic P2X7 Receptors as Therapeutic Targets in Interstitial Cystitis\/Bladder Pain Syndrome; Key Role of ATP Signaling in Inflammation","volume":"6","author":"Taidi","year":"2019","journal-title":"Bladder"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Liu, J., Liu, S., Hu, S., Lu, J., Wu, C., Hu, D., and Zhang, W. (2023). ATP Ion Channel P2X Purinergic Receptors in Inflammation Response. Biomed. Pharmacother., 158.","DOI":"10.1016\/j.biopha.2022.114205"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1590\/s1677-5538.ibju.2020.1104","article-title":"Exploration of the Core Genes in Ulcerative Interstitial Cystitis\/Bladder Pain Syndrome","volume":"47","author":"Wu","year":"2021","journal-title":"Int. Braz. J. Urol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4100","DOI":"10.21037\/tau-21-657","article-title":"Neuroinflammatory Gene Expression Analysis Reveals Potential Novel Mediators and Treatment Targets in Interstitial Cystitis with Hunner Lesions","volume":"10","author":"Werneburg","year":"2021","journal-title":"Transl. Androl. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"101114","DOI":"10.1016\/j.xcrm.2023.101114","article-title":"Genome-Wide Association Study Identifies Risk Loci within the Major Histocompatibility Complex Region for Hunner-Type Interstitial Cystitis","volume":"4","author":"Akiyama","year":"2023","journal-title":"Cell Rep. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1097\/JU.0000000000002278","article-title":"Overexpression of HIF1\u03b1 in Hunner Lesions of Interstitial Cystitis: Pathophysiological Implications","volume":"207","author":"Akiyama","year":"2022","journal-title":"J. Urol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/s11302-013-9395-y","article-title":"Purinergic Signalling in the Urinary Tract in Health and Disease","volume":"10","author":"Burnstock","year":"2014","journal-title":"Purinergic Signal"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.3390\/cimb46020073","article-title":"Next Generation Sequencing and Electromyography Reveal the Involvement of the P2RX6 Gene in Myopathy","volume":"46","author":"Vinci","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"C27","DOI":"10.1152\/ajpcell.00552.2004","article-title":"Augmented Extracellular ATP Signaling in Bladder Urothelial Cells from Patients with Interstitial Cystitis","volume":"290","author":"Sun","year":"2006","journal-title":"Am. J. Physiol.-Cell Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/s41585-023-00850-y","article-title":"Mechanisms of Oxidative Stress in Interstitial Cystitis\/Bladder Pain Syndrome","volume":"21","author":"Mohammad","year":"2024","journal-title":"Nat. Rev. Urol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3799","DOI":"10.1002\/1873-3468.13966","article-title":"Structures of ABC Transporters: Handle with Care","volume":"594","author":"Lewinson","year":"2020","journal-title":"FEBS Lett."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"103537","DOI":"10.1016\/j.drudis.2023.103537","article-title":"ATP-Binding Cassette Efflux Transporters and MDR in Cancer","volume":"28","author":"Pote","year":"2023","journal-title":"Drug Discov. Today"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1146\/annurev-biochem-011520-105201","article-title":"Structural and Mechanistic Principles of ABC Transporters","volume":"89","author":"Thomas","year":"2020","journal-title":"Annu. Rev. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1111\/IGC.0b013e3181a835fc","article-title":"Relationship Between ABCF2 Expression and Response to Chemotherapy or Prognosis in Clear Cell Adenocarcinoma of the Ovary","volume":"20","author":"Tsuda","year":"2010","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/S0022-5347(01)61948-7","article-title":"The Diagnosis of Interstitial Cystitis Revisited: Lessons Learned From The National Institutes Of Health Interstitial Cystitis Database Study","volume":"161","author":"Hanno","year":"1999","journal-title":"J. Urol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1007\/s00192-020-04512-0","article-title":"Does Cystoscopy Method Affect the Investigation of Bladder Pain Syndrome\/Interstitial Cystitis?","volume":"32","author":"Tailor","year":"2021","journal-title":"Int. Urogynecol. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.urology.2009.05.044","article-title":"Elevated Urinary Levels and Urothelial Expression of Hepatocarcinoma-Intestine-Pancreas\/Pancreatitis-Associated Protein in Patients with Interstitial Cystitis","volume":"75","author":"Makino","year":"2010","journal-title":"Urology"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Vinci, M., Greco, D., Figura, M.G., Treccarichi, S., Musumeci, A., Greco, V., Pettinato, R., Gloria, A., Papa, C., and Saccone, S. (2024). Exploring the Role of FICD, a New Potential Gene Involved in Borderline Intellectual Functioning, Psychological and Metabolic Disorders. Genes, 15.","DOI":"10.3390\/genes15121655"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Cal\u00ec, F., Vinci, M., Treccarichi, S., Papa, C., Gloria, A., Musumeci, A., Federico, C., Vitello, G.A., Nicotera, A.G., and Di Rosa, G. (2024). PLEKHG1: New Potential Candidate Gene for Periventricular White Matter Abnormalities. Genes, 15.","DOI":"10.3390\/genes15081096"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1111\/j.1464-410X.2007.07082.x","article-title":"A prospective, single-blind, randomized crossover trial of sacral vs pudendal nerve stimulation for interstitial cystitis","volume":"100","author":"Peters","year":"2007","journal-title":"BJU Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.tig.2015.03.013","article-title":"Somatic Mosaicism: Implications for Disease and Transmission Genetics","volume":"31","author":"Campbell","year":"2015","journal-title":"Trends Genet."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Mohiuddin, M., Kooy, R.F., and Pearson, C.E. (2022). De Novo Mutations, Genetic Mosaicism and Human Disease. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.983668"},{"key":"ref_31","first-page":"67","article-title":"Effect of Mouse Ovarian Vitrification on Promoter Methylation of Inhba and Inhbb in Granulosa Cells of Follicles","volume":"42","author":"Damavandi","year":"2021","journal-title":"Cryo Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.nbd.2014.05.007","article-title":"ATP-Binding Cassette Transporter A1: From Metabolism to Neurodegeneration","volume":"72","author":"Koldamova","year":"2014","journal-title":"Neurobiol. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/s00018-022-04510-z","article-title":"Excess Intracellular ATP Causes Neuropathic Pain Following Spinal Cord Injury","volume":"79","author":"Nakajima","year":"2022","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.euf.2020.02.014","article-title":"A Systematic Review of Surgical Interventions for the Treatment of Bladder Pain Syndrome\/Interstitial Cystitis","volume":"7","author":"Osman","year":"2021","journal-title":"Eur. Urol. Focus."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1515\/revneuro-2017-0007","article-title":"Mast Cells in Neuropathic Pain: An Increasing Spectrum of Their Involvement in Pathophysiology","volume":"28","author":"Kaur","year":"2017","journal-title":"Rev. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1097\/01.ju.0000092945.76827.47","article-title":"Gene Therapy for Bladder Pain with Gene Gun Particle Encoding Pro-Opiomelanocortin CDNA","volume":"170","author":"Chuang","year":"2003","journal-title":"J. Urol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1097\/j.pain.0000000000001750","article-title":"A Functional Polymorphism in the ATP-Binding Cassette B1 Transporter Predicts Pharmacologic Response to Combination of Nortriptyline and Morphine in Neuropathic Pain Patients","volume":"161","author":"Benavides","year":"2020","journal-title":"Pain"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/3\/281\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:43:06Z","timestamp":1760028186000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/3\/281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,26]]},"references-count":37,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["genes16030281"],"URL":"https:\/\/doi.org\/10.3390\/genes16030281","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,26]]}}}