{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T12:02:37Z","timestamp":1784376157575,"version":"3.55.0"},"reference-count":25,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"vor","delay-in-days":198,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Mutation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Purinergic P2X receptors (\n                      <jats:italic>P2RX<\/jats:italic>\n                      ) play key roles in neuroinflammatory processes through ATP\u2010gated ion channel signaling. Dysregulation of\n                      <jats:italic>P2RX<\/jats:italic>\n                      receptor activity has been implicated in maternal immune activation, mitochondrial dysfunction, oxidative stress, and synaptic abnormalities associated with autism spectrum disorder (ASD). Despite increasing mechanistic evidence, the contribution of\n                      <jats:italic>P2RX<\/jats:italic>\n                      gene variants to ASD remains poorly understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We retrospectively evaluated whole\u2010exome sequencing (WES) data from individuals diagnosed with ASD according to DSM\u20105 criteria. Variants in the\n                      <jats:italic>P2RX1\u2013P2RX7<\/jats:italic>\n                      genes were identified. Clinical, genetic, and in silico data were reviewed, and variants were classified according to ACMG\/AMP guidelines.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eleven individuals were identified with heterozygous\n                      <jats:italic>P2RX<\/jats:italic>\n                      variants, most frequently in\n                      <jats:italic>P2RX7<\/jats:italic>\n                      (54.5%), followed by\n                      <jats:italic>P2RX5<\/jats:italic>\n                      (27.3%) and\n                      <jats:italic>P2RX4<\/jats:italic>\n                      (18.2%). Core clinical features across all genes included ASD, intellectual disability (ID), and epilepsy.\n                      <jats:italic>P2RX4<\/jats:italic>\n                      variants included an in\u2010frame deletion (p.Ile322del) and a truncating variant (p.Tyr366LeufsTer7), both observed in individuals with ASD and ID.\n                      <jats:italic>P2RX5<\/jats:italic>\n                      variants comprised rare missense substitutions with variable in silico pathogenicity. Several\n                      <jats:italic>P2RX7<\/jats:italic>\n                      variants, most notably the canonical splice\u2010site variant c.614 + 1G &gt; A fulfilling ACMG\/AMP PVS1 and PM2 criteria, were predicted to alter receptor function. Overall, in silico analyses indicated moderate to high predicted functional impact; however, most variants lacked segregation and functional validation data.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings provide preliminary, exploratory observations suggesting that rare\n                      <jats:italic>P2RX<\/jats:italic>\n                      variants may represent biologically plausible candidates relevant to ASD\u2010related pathways; however, no conclusions regarding disease association or causality can be drawn. These findings should be considered hypothesis\u2010generating and require validation through larger controlled genetic studies and functional investigations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/humu\/5522396","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T11:08:56Z","timestamp":1784372936000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rare Variants in Purinergic P2X Receptor Genes\n                    <i>(P2RX4, P2RX5, P2RX7)<\/i>\n                    in Individuals With Autism Spectrum Disorder: An Exploratory Study"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4574-421X","authenticated-orcid":false,"given":"G\u00fcl","family":"\u00dcnsel-Bolat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6574-8149","authenticated-orcid":false,"given":"Hilmi","family":"Bolat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,18]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4930-11.2012"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2022.03.009"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0041229"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2017.07.155"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-017-9579-y"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02601-z"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1082"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep23286"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2024.07.047"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2007.08.007"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.04.051"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbih.2025.101037"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0057380"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2022.01.015"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp324"},{"key":"e_1_2_9_16_2","unstructured":"GarrisonE.andMarthG. Haplotype-Based Variant Detection From Short-Read Sequencing 2012 arXiv preprint arXiv:1207.3907https:\/\/doi.org\/10.48550\/arXiv.1207.3907."},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0974-4"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2013.98"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2011.07763.x"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2011.02.003"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.1069"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/2040-2392-6-1"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.424"},{"key":"e_1_2_9_25_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12991-023-00477-8"}],"container-title":["Human Mutation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/humu\/5522396","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/humu\/5522396","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/humu\/5522396","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T11:08:57Z","timestamp":1784372937000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/humu\/5522396"}},"subtitle":[],"editor":[{"given":"Miklos","family":"Sahin -Toth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":25,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/humu\/5522396"],"URL":"https:\/\/doi.org\/10.1155\/humu\/5522396","archive":["Portico"],"relation":{},"ISSN":["1059-7794","1098-1004"],"issn-type":[{"value":"1059-7794","type":"print"},{"value":"1098-1004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2026-03-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"5522396"}}