{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T06:26:57Z","timestamp":1772000817534,"version":"3.50.1"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>\n                    Leukoencephalopathy with ataxia (LKPAT), also known as\n                    <jats:italic>CLCN2<\/jats:italic>\n                    -related leukoencephalopathy, is a rare autosomal recessive disorder caused by pathogenic variants in\n                    <jats:italic>CLCN2,<\/jats:italic>\n                    which encodes ClC-2, a ubiquitously expressed chloride channel protein. However, due to high variability in clinical presentation leading to underdiagnosis, very few cases have been reported since its first description in 2013. The prevalence and genotype\u2013phenotype correlations of LKPAT remain unclear, as do the pathogenic mechanisms of\n                    <jats:italic>CLCN2<\/jats:italic>\n                    variants. In this study, we reported a Chinese man who presented with dizziness, weakness of the left lower limb, and mild cerebellar ataxia. Notably, the patient had a history of azoospermia. Brain MRI showed symmetrical and confluent white matter abnormalities with hypointense signals on T1-weighted images and hyperintense signals on T2-weighted images. In this patient, a novel biallelic missense variant p.A506V was identified in\n                    <jats:italic>CLCN2<\/jats:italic>\n                    . Through\n                    <jats:italic>in silico<\/jats:italic>\n                    analysis, we observed that substitution of A506 with V506 altered hydrogen bond formation at chloride-binding sites. In addition, the A506V variant impacted the interaction of ClC-2 with GlialCAM, a ClC-2 auxiliary subunit that can physically bind ClC-2 and regulate its biophysical properties and subcellular localization in glial cells. Furthermore, we reviewed the literature and identified potential genotype\u2013phenotype correlations in\n                    <jats:italic>CLCN2<\/jats:italic>\n                    -related diseases. Our results highlight the need for\n                    <jats:italic>CLCN2<\/jats:italic>\n                    genetic analysis to establish a definitive diagnosis when strong diagnostic clues are present. This study expands the genotypic spectrum of LKPAT, indicates the potential pathogenesis of the\n                    <jats:italic>CLCN2<\/jats:italic>\n                    A506V variant, and provides valuable insights into further investigation into therapeutics of\n                    <jats:italic>CLCN2<\/jats:italic>\n                    -related leukoencephalopathy.\n                  <\/jats:p>","DOI":"10.3389\/fgene.2026.1761205","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T05:33:23Z","timestamp":1771997603000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of a novel CLCN2 homozygous variant in a man with leukoencephalopathy and infertility: a case report and literature review"],"prefix":"10.3389","volume":"17","author":[{"given":"Lijia","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Neurology, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]},{"name":"Department of Neurology, Shanghai Tongji Hospital, School of Medicine, Tongji University","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiqing","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjiong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Shanghai Sixth People\u2019s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1007\/s00247-022-05577-3","article-title":"Brain imaging findings in CLCN2-related leukoencephalopathy","volume":"53","author":"Abreu","year":"2023","journal-title":"Pediatr. Radiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"100189","DOI":"10.1016\/j.prdoa.2023.100189","article-title":"Co-occurrence of CLCN2-related leukoencephalopathy and SPG56","volume":"8","author":"Almasoudi","year":"2023","journal-title":"Clin. Park Relat. Disord."},{"key":"B3","doi-asserted-by":"publisher","first-page":"107918","DOI":"10.1016\/j.parkreldis.2025.107918","article-title":"CLCN2-related leukoencephalopathy with ataxia (LKPAT) and dystonia in two unrelated Indian patients","volume":"137","author":"Bavdhankar","year":"2025","journal-title":"Park. Relat. Disord."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e6737","DOI":"10.1002\/ccr3.6737","article-title":"A Tunisian patient with CLCN2-related leukoencephalopathy","volume":"10","author":"Ben Mohamed","year":"2022","journal-title":"Clin. Case Rep."},{"key":"B5","doi-asserted-by":"publisher","first-page":"6581","DOI":"10.1523\/JNEUROSCI.0338-07.2007","article-title":"Leukoencephalopathy upon disruption of the chloride channel ClC-2","volume":"27","author":"Blanz","year":"2007","journal-title":"J. Neurosci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1093\/emboj\/20.6.1289","article-title":"Male germ cells and photoreceptors, both dependent on close cell-cell interactions, degenerate upon ClC-2 Cl(-) channel disruption","volume":"20","author":"Bosl","year":"2001","journal-title":"EMBO J."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21124391","article-title":"Fragile X-Associated tremor\/ataxia syndrome (FXTAS): pathophysiology and clinical implications","volume":"21","author":"Cabal-Herrera","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"127574","DOI":"10.1016\/j.ijbiomac.2023.127574","article-title":"Promising effects of beta-glucans on gelation in protein-based products: a review","volume":"256","author":"Cao","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"2002","DOI":"10.1002\/mds.30290","article-title":"Prevalence of NOTCH2NLC and FMR1 repeat expansions in atypical parkinsonism compared to asymptomatic elderly individuals","volume":"40","author":"Chen","year":"2025","journal-title":"Mov. Disord."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1278961","DOI":"10.3389\/fgene.2023.1278961","article-title":"Case report: a frameshift mutation in CLCN2-related leukoencephalopathy and retinopathy","volume":"14","author":"Cheng","year":"2023","journal-title":"Front. Genet."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1212\/01.wnl.0000239837.57475.3a","article-title":"Molecular and imaging correlates of the fragile X-associated tremor\/ataxia syndrome","volume":"67","author":"Cohen","year":"2006","journal-title":"Neurology"},{"key":"B12","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1001\/jama.1993.03500180078038","article-title":"Population-based norms for the mini-mental state examination by age and educational level","volume":"269","author":"Crum","year":"1993","journal-title":"JAMA"},{"key":"B13","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1016\/S1474-4422(13)70053-X","article-title":"Brain white matter oedema due to ClC-2 chloride channel deficiency: an observational analytical study","volume":"12","author":"Depienne","year":"2013","journal-title":"Lancet Neurol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1217","DOI":"10.1212\/WNL.0000000000000812","article-title":"Subclinical leukodystrophy and infertility in a man with a novel homozygous CLCN2 mutation","volume":"83","author":"Di Bella","year":"2014","journal-title":"Neurology"},{"key":"B15","doi-asserted-by":"publisher","first-page":"932760","DOI":"10.3389\/fgene.2022.932760","article-title":"Genotypic and phenotypic characteristics of 12 chinese children with glycogen storage diseases","volume":"13","author":"Dong","year":"2022","journal-title":"Front. Genet."},{"key":"B16","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1126\/science.1082708","article-title":"Gating the selectivity filter in ClC chloride channels","volume":"300","author":"Dutzler","year":"2003","journal-title":"Science"},{"key":"B17","doi-asserted-by":"publisher","first-page":"2146","DOI":"10.1212\/WNL.0000000000001612","article-title":"White matter disease and cognitive impairment in FMR1 premutation carriers","volume":"84","author":"Filley","year":"2015","journal-title":"Neurology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/0022-3956(75)90026-6","article-title":"Mini-mental state a practical method for grading the cognitive state of patients for the clinician","volume":"12","author":"Folstein","year":"1975","journal-title":"J. Psychiatr. Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"6993","DOI":"10.1113\/JP275087","article-title":"Leukoencephalopathy-causing CLCN2 mutations are associated with impaired Cl(-) channel function and trafficking","volume":"595","author":"Gaitan-Penas","year":"2017","journal-title":"J. Physiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e209702","DOI":"10.1212\/WNL.0000000000209702","article-title":"Distinctive imaging features in a tremulous patient with CLCN2-Related leukoencephalopathy","volume":"103","author":"Garg","year":"2024","journal-title":"Neurology"},{"key":"B21","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1136\/jnnp-2016-315525","article-title":"A novel homozygous change of CLCN2 (p.His590Pro) is associated with a subclinical form of leukoencephalopathy with ataxia (LKPAT)","volume":"88","author":"Giorgio","year":"2017","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B22","doi-asserted-by":"publisher","first-page":"100074","DOI":"10.1074\/jbc.RA120.016031","article-title":"Cellular basis of ClC-2 Cl(-) channel-related brain and testis pathologies","volume":"296","author":"Goppner","year":"2021","journal-title":"J. Biol. Chem."},{"key":"B23","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1038\/360759a0","article-title":"Regions involved in the opening of CIC-2 chloride channel by voltage and cell volume","volume":"360","author":"Grunder","year":"1992","journal-title":"Nature"},{"key":"B24","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1186\/s12883-019-1390-7","article-title":"CLCN2-related leukoencephalopathy: a case report and review of the literature","volume":"19","author":"Guo","year":"2019","journal-title":"BMC Neurol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"544","DOI":"10.1016\/j.parkreldis.2015.02.013","article-title":"Secondary paroxysmal kinesigenic dyskinesia associated with CLCN2 gene mutation","volume":"21","author":"Hanagasi","year":"2015","journal-title":"Park. Relat. Disord."},{"key":"B26","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1093\/brain\/awq368","article-title":"A voxel-based morphometry study of grey matter loss in fragile X-associated tremor\/ataxia syndrome","volume":"134","author":"Hashimoto","year":"2011","journal-title":"Brain"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3475","DOI":"10.1038\/ncomms4475","article-title":"Disrupting MLC1 and GlialCAM and ClC-2 interactions in leukodystrophy entails glial chloride channel dysfunction","volume":"5","author":"Hoegg-Beiler","year":"2014","journal-title":"Nat. Commun."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1002\/mdc3.13783","article-title":"CLCN2-Related leukoencephalopathy in two unrelated patients due to novel variants","volume":"10","author":"Holla","year":"2023","journal-title":"Mov. Disord. Clin. Pract."},{"key":"B29","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.braindev.2018.07.011","article-title":"A novel homozygous mutation of CLCN2 in a patient with characteristic brain MRI images - a first case of CLCN2-related leukoencephalopathy in Japan","volume":"41","author":"Hoshi","year":"2019","journal-title":"Brain Dev."},{"key":"B30","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1086\/374321","article-title":"Fragile X premutation tremor\/ataxia syndrome: molecular, clinical, and neuroimaging correlates","volume":"72","author":"Jacquemont","year":"2003","journal-title":"Am. J. Hum. Genet."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1152\/physrev.00047.2017","article-title":"CLC chloride channels and transporters: structure, function, physiology, and disease","volume":"98","author":"Jentsch","year":"2018","journal-title":"Physiol. Rev."},{"key":"B32","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1016\/j.neuron.2011.12.039","article-title":"GlialCAM, a protein defective in a leukodystrophy, serves as a ClC-2 Cl(-) channel auxiliary subunit","volume":"73","author":"Jeworutzki","year":"2012","journal-title":"Neuron"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1093\/emboj\/16.7.1582","article-title":"Molecular dissection of gating in the ClC-2 chloride channel","volume":"16","author":"Jordt","year":"1997","journal-title":"EMBO J."},{"key":"B34","doi-asserted-by":"publisher","first-page":"3424","DOI":"10.1038\/s41467-023-39218-6","article-title":"Cryo-EM structures of ClC-2 chloride channel reveal the blocking mechanism of its specific inhibitor AK-42","volume":"14","author":"Ma","year":"2023","journal-title":"Nat. Commun."},{"key":"B35","doi-asserted-by":"publisher","first-page":"e1007530","DOI":"10.1371\/journal.pcbi.1007530","article-title":"Dynamical model of the CLC-2 ion channel reveals conformational changes associated with selectivity-filter gating","volume":"16","author":"McKiernan","year":"2020","journal-title":"PLoS Comput. Biol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1002\/humu.23946","article-title":"A diagnostic ceiling for exome sequencing in cerebellar ataxia and related neurological disorders","volume":"41","author":"Ngo","year":"2020","journal-title":"Hum. Mutat."},{"key":"B37","doi-asserted-by":"publisher","first-page":"fcad273","DOI":"10.1093\/braincomms\/fcad273","article-title":"Expanding the phenotypic spectrum of CLCN2-related leucoencephalopathy and ataxia","volume":"6","author":"N\u00f3brega","year":"2024","journal-title":"Brain Commun."},{"key":"B38","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1186\/s12883-024-03919-2","article-title":"CLCN2-related leukoencephalopathy with novel compound heterozygous variants followed with magnetic resonance imaging over 17 years: a case report","volume":"24","author":"Ohira","year":"2024","journal-title":"BMC Neurol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"123486","DOI":"10.1016\/j.jns.2025.123486","article-title":"Clinical, neuroimaging and genetic findings in the Japanese case series of CLCN2-related leukoencephalopathy","volume":"472","author":"Orimo","year":"2025","journal-title":"J. Neurol. Sci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1016\/j.braindev.2020.02.008","article-title":"A case of CLCN2-related leukoencephalopathy with bright tree appearance during aseptic meningitis","volume":"42","author":"Ozaki","year":"2020","journal-title":"Brain Dev."},{"key":"B41","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1177\/0883073820904294","article-title":"Leukodystrophies and genetic leukoencephalopathies in children specified by exome sequencing in an expanded gene panel","volume":"35","author":"Parayil Sankaran","year":"2020","journal-title":"J. Child. Neurol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1038\/nature20812","article-title":"Structure of a CLC chloride ion channel by cryo-electron microscopy","volume":"541","author":"Park","year":"2017","journal-title":"Nature"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1352947","DOI":"10.3389\/fgene.2024.1352947","article-title":"Megalencephalic leukoencephalopathy with subcortical cysts: a variant update and review of the literature","volume":"15","author":"Passchier","year":"2024","journal-title":"Front. Genet."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1093\/bioinformatics\/btu097","article-title":"ZDOCK server: interactive docking prediction of protein-protein complexes and symmetric multimers","volume":"30","author":"Pierce","year":"2014","journal-title":"Bioinformatics"},{"key":"B45","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1016\/j.neuroscience.2009.10.028","article-title":"Molecular disruptions of the panglial syncytium block potassium siphoning and axonal saltatory conduction: pertinence to neuromyelitis optica and other demyelinating diseases of the central nervous system","volume":"168","author":"Rash","year":"2010","journal-title":"Neuroscience"},{"key":"B46","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1161\/HYPERTENSIONAHA.121.16498","article-title":"Genetics of primary aldosteronism","volume":"79","author":"Scholl","year":"2022","journal-title":"Hypertension"},{"key":"B47","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/s41588-018-0048-5","article-title":"CLCN2 chloride channel mutations in familial hyperaldosteronism type II","volume":"50","author":"Scholl","year":"2018","journal-title":"Nat. Genet."},{"key":"B48","first-page":"589","article-title":"Leukoencephalopathy with ataxia caused by mutation of CLCN2 gene: one case report","volume":"54","author":"Shi","year":"2021","journal-title":"Chin. J. Neurol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"3170","DOI":"10.1093\/brain\/aww249","article-title":"Clinicopathological features of adult-onset neuronal intranuclear inclusion disease","volume":"139","author":"Sone","year":"2016","journal-title":"Brain"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1038\/s41588-019-0459-y","article-title":"Long-read sequencing identifies GGC repeat expansions in NOTCH2NLC associated with neuronal intranuclear inclusion disease","volume":"51","author":"Sone","year":"2019","journal-title":"Nat. Genet."},{"key":"B51","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1007\/s11906-019-0934-y","article-title":"Pathogenesis of familial hyperaldosteronism type II: new concepts involving anion channels","volume":"21","author":"Stowasser","year":"2019","journal-title":"Curr. Hypertens. Rep."},{"key":"B52","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/356057a0","article-title":"A chloride channel widely expressed in epithelial and non-epithelial cells","volume":"356","author":"Thiemann","year":"1992","journal-title":"Nature"},{"key":"B53","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1148\/radiol.2412051345","article-title":"Childhood white matter disorders: quantitative MR imaging and spectroscopy","volume":"241","author":"van der Voorn","year":"2006","journal-title":"Radiology"},{"key":"B54","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1016\/0092-8674(91)90397-h","article-title":"Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome","volume":"65","author":"Verkerk","year":"1991","journal-title":"Cell"},{"key":"B55","doi-asserted-by":"publisher","first-page":"11","DOI":"10.3892\/mmr.2017.6600","article-title":"Research and progress on ClC-2","volume":"16","author":"Wang","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"B56","doi-asserted-by":"publisher","first-page":"125535","DOI":"10.1016\/j.talanta.2023.125535","article-title":"An efficient and universal in silico screening strategy for acquisition of high-affinity aptamer and its application in analytical utility","volume":"269","author":"Wang","year":"2024","journal-title":"Talanta"},{"key":"B57","doi-asserted-by":"publisher","first-page":"2364","DOI":"10.1093\/brain\/awac426","article-title":"The genetic and phenotypic spectra of adult genetic leukoencephalopathies in a cohort of 309 patients","volume":"146","author":"Wu","year":"2023","journal-title":"Brain"},{"key":"B58","doi-asserted-by":"publisher","first-page":"1281","DOI":"10.1007\/s00234-019-02257-2","article-title":"Identifying patients with neuronal intranuclear inclusion disease in Singapore using characteristic diffusion-weighted MR images","volume":"61","author":"Yu","year":"2019","journal-title":"Neuroradiology"},{"key":"B59","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1113\/jphysiol.2005.102392","article-title":"Removal of gating in voltage-dependent ClC-2 chloride channel by point mutations affecting the pore and C-terminus CBS-2 domain","volume":"572","author":"Yusef","year":"2006","journal-title":"J. Physiol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1159\/000478089","article-title":"Identification of 3 novel patients with CLCN2-Related leukoencephalopathy due to CLCN2 mutations","volume":"78","author":"Zeydan","year":"2017","journal-title":"Eur. Neurol."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1740","DOI":"10.1002\/humu.23335","article-title":"Mutations in KARS cause early-onset hearing loss and leukoencephalopathy: potential pathogenic mechanism","volume":"38","author":"Zhou","year":"2017","journal-title":"Hum. Mutat."},{"key":"B62","doi-asserted-by":"publisher","first-page":"82","DOI":"10.3760\/cma.j.cn511374-20241014-00533","article-title":"Genetic analysis of a child with leukoencephalopathy with ataxia caused by a homozygous variant of CLCN2 gene and a literature review","volume":"42","author":"Zhou","year":"2025","journal-title":"Zhonghua Yi Xue Yi Chuan Xue Za Zhi"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1761205\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T05:33:24Z","timestamp":1771997604000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1761205\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,25]]},"references-count":62,"alternative-id":["10.3389\/fgene.2026.1761205"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2026.1761205","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,25]]},"article-number":"1761205"}}