{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:03:18Z","timestamp":1791201798036,"version":"4.2.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":277,"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"}],"funder":[{"DOI":"10.13039\/501100007289","name":"Nanjing Medical University","doi-asserted-by":"publisher","award":["KJCXZ2024004"],"award-info":[{"award-number":["KJCXZ2024004"]}],"id":[{"id":"10.13039\/501100007289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20241732"],"award-info":[{"award-number":["BK20241732"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"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>Objective<\/jats:title>\n                    <jats:p>\n                      <jats:italic>PRRT2<\/jats:italic>\n                      mutations are associated with a wide spectrum of paroxysmal neurologic disorders. In this study, we analyze clinical and genetic data from a large pediatric cohort to define genotype\u2013phenotype correlations and to provide a basis for individualized genetic counseling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This retrospective study included 103 children with\n                      <jats:italic>PRRT2<\/jats:italic>\n                      mutations treated at the Children\u2032s Hospital Affiliated to Nanjing Medical University from August 2018 to August 2023. Detailed clinical data and genetic results were collected and systematically analyzed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among the 103 children, self\u2010limited familial infantile epilepsy (SeLFIE) was the most common phenotype. A total of 26 different\n                      <jats:italic>PRRT2<\/jats:italic>\n                      mutations were identified, 93.2% of which were predicted loss\u2010of\u2010function (LOF) mutations. These mutations were highly enriched in the N\u2010terminal cytoplasmic region of the protein, particularly in the proline\u2010rich domain. Predicted LOF mutations accounted for nearly all cases of SeLFIE and infantile convulsions with paroxysmal choreoathetosis. Clinical features, including age of onset, rates of abnormal EEG and brain MRI findings, and treatment response, showed a gradient across the three phenotypic groups, with the most pronounced abnormalities in SeLFIE and the mildest in paroxysmal kinesigenic dyskinesia. Additionally, 12 novel variants were identified.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      This study confirms that\n                      <jats:italic>PRRT2<\/jats:italic>\n                      \u2010associated disorders are primarily driven by predicted LOF mutations and, using a large cohort, establishes a genotype\u2010phenotype\u2010treatment response continuum model based on residual PRRT2 protein activity. This model provides a critical framework for prognosis assessment and personalized genetic counseling.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/humu\/8968480","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:38:33Z","timestamp":1791200313000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genotype\u2013Phenotype Correlations and Their Implications for Personalized Genetic Counseling in 103 Patients With\n                    <i>PRRT2<\/i>\n                    Mutations"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-9789-0325","authenticated-orcid":false,"given":"Shangyu","family":"Wang","sequence":"first","affiliation":[{"name":"Medical School Nanjing University  Nanjing China  nju.edu.cn"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7254-1465","authenticated-orcid":false,"given":"Xiaohui","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Neurology Children\u2032s Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gege","family":"Yuan","sequence":"additional","affiliation":[{"name":"Nanjing Key Laboratory of Pediatrics Children\u2032s Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingying","family":"He","sequence":"additional","affiliation":[{"name":"Department of Neurology Children\u2032s Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurology Children\u2032s Hospital of Nanjing Medical 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