{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T04:56:45Z","timestamp":1790571405500,"version":"4.1.0"},"reference-count":19,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100010805","name":"Forskningsr\u00e5det i Syd\u00f6stra Sverige","doi-asserted-by":"publisher","award":["1012769"],"award-info":[{"award-number":["1012769"]}],"id":[{"id":"10.13039\/100010805","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Rett syndrome (RTT) is a neurodevelopmental disorder mainly affecting females and may start with seemingly normal early development but leads to developmental stagnation, regression, and characteristic neurological symptoms. While most cases involve\n                      <jats:italic>MECP2<\/jats:italic>\n                      variants, other genes have been implicated in RTT and RTT\u2010like phenotypes, but the underlying molecular mechanisms remain incompletely understood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We describe a girl fulfilling the clinical diagnostic criteria for classic RTT in whom standard genetic testing, including\n                      <jats:italic>MECP2<\/jats:italic>\n                      and\n                      <jats:italic>CDKL5<\/jats:italic>\n                      , was normal. Trio\u2010based whole\u2010exome sequencing was used to identify an alternative genetic cause that was confirmed using Sanger sequencing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A heterozygous\n                      <jats:italic>de novo<\/jats:italic>\n                      variant in\n                      <jats:italic>GABBR2<\/jats:italic>\n                      (NM_005458.7:c.1699G&gt;A; p.Ala567Thr) was identified as the only clinically relevant genetic finding. The patient fulfilled the clinical diagnostic criteria for classic RTT and exhibited developmental stagnation, progressive impairment of purposeful hand use, characteristic stereotypic movements, autonomic dysfunction, and behavioral disturbances.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This patient expands the phenotypic spectrum associated with\n                      <jats:italic>GABBR2<\/jats:italic>\n                      variants and, together with previously reported cases, provides further evidence that\n                      <jats:italic>GABBR2<\/jats:italic>\n                      \u2010related disease may present with a clinical RTT phenotype. These findings support a role for\n                      <jats:italic>GABBR2<\/jats:italic>\n                      \u2010mediated GABAergic signaling in the pathophysiology of RTT and highlight the importance of considering\n                      <jats:italic>GABBR2<\/jats:italic>\n                      in the genetic evaluation of\n                      <jats:italic>MECP2<\/jats:italic>\n                      \u2010negative patients with a clinical RTT phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mgg3.70303","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T04:36:30Z","timestamp":1790570190000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Heterozygous Variant in the\n                    <scp>GABBR2<\/scp>\n                    Gene in a Girl With Clinical Classic Rett Syndrome"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6387-8507","authenticated-orcid":false,"given":"Jenny","family":"Klintenstedt","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics, and Department of Biomedical and Clinical Sciences Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0641-3834","authenticated-orcid":false,"given":"Peter","family":"Baeck","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Kalmar County Hospital  Kalmar Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingegerd Witt","family":"Engerstr\u00f6m","sequence":"additional","affiliation":[{"name":"National Swedish Rett Center J\u00e4mtland County Council  \u00d6stersund Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9474-6820","authenticated-orcid":false,"given":"Cecilia","family":"Gunnarsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, and Department of Biomedical and Clinical Sciences Link\u00f6ping University  Link\u00f6ping Sweden"},{"name":"Center for Rare Diseases in Southeast Region of Sweden Link\u00f6ping University  Link\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"StatPearls","author":"Bounds C. 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