{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:03:34Z","timestamp":1789625014283,"version":"build-2803163510"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"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. Pediatr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Early-onset parkinsonism is often associated with genetic factors. Pathogenic variants in the\n                      <jats:italic>FBXO7<\/jats:italic>\n                      gene are a rare cause of early-onset parkinsonism, typically presenting as parkinsonian-pyramidal syndrome (PPS), also known as Parkinson's disease-15 (PARK15). To date, only three cases of infantile-onset PARK15 have been reported worldwide. Herein, we describe a Chinese patient with neonatal-onset PARK15, who carried novel compound heterozygous\n                      <jats:italic>FBXO7<\/jats:italic>\n                      variants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      A 37-hour-old male infant with generalized limb rigidity was referred for evaluation of neonatal-onset hypertonia. Physical examination revealed abnormal vocalization, poor sucking and swallowing (requiring nasogastric tube feeding), and abdominal muscle rigidity. Pyramidal involvement was evidenced by positive Babinski sign and its equivalents, together with hyperreflexia, while extrapyramidal findings included lead-pipe rigidity of all four limbs with markedly increased muscle tone. Whole-exome sequencing identified two compound heterozygous nonsense variants in\n                      <jats:italic>FBXO7<\/jats:italic>\n                      , c.376G\u2009&amp;gt;\u2009T (p.Gly126*) and c.1033C\u2009&amp;gt;\u2009T (p.Arg345*), inherited from the father and mother, respectively. Both variants were classified as pathogenic. Following diagnosis, the parents elected to discontinue active in-hospital treatment, and the infant was discharged home. Nevertheless, a trial of oral levodopa was initiated at home. Despite levodopa treatment, the infant showed no clinical improvement and died at 89 days of age.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      To our knowledge, this is the first reported case of neonatal-onset PARK15 caused by\n                      <jats:italic>FBXO7<\/jats:italic>\n                      variants. This case expands the mutational and clinical spectrum of PARK15 in the neonatal period.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1934625","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:31:04Z","timestamp":1789623064000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Neonatal-onset parkinsonian-pyramidal syndrome caused by novel compound heterozygous FBXO7 variants"],"prefix":"10.3389","volume":"14","author":[{"given":"Weicong","family":"Pu","sequence":"first","affiliation":[{"name":"Department of Neonatology, Children\u2019s Hospital of Hebei Province","place":["Shijiazhuang, China"]},{"name":"Pediatric Clinical Research Centre of Hebei Province, Children's Hospital of Hebei Province","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zelei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Children\u2019s Hospital of Hebei Province","place":["Shijiazhuang, China"]},{"name":"Pediatric Clinical Research Centre of Hebei Province, Children's Hospital of Hebei Province","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Cao","sequence":"additional","affiliation":[{"name":"Pediatric Clinical Research Centre of Hebei Province, Children's Hospital of Hebei Province","place":["Shijiazhuang, China"]},{"name":"Genomic Medicine Research Laboratory, Children\u2019s Hospital of Hebei Province","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiancheng","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Children\u2019s Hospital of Hebei Province","place":["Shijiazhuang, China"]},{"name":"Pediatric Clinical Research Centre of Hebei Province, Children's Hospital of Hebei Province","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Children\u2019s Hospital of Hebei Province","place":["Shijiazhuang, China"]},{"name":"Pediatric Clinical Research Centre of Hebei Province, Children's Hospital of Hebei Province","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Children\u2019s Hospital of Hebei Province","place":["Shijiazhuang, China"]},{"name":"Pediatric Clinical Research Centre of Hebei Province, Children's Hospital of Hebei Province","place":["Shijiazhuang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1111\/ane.12616","article-title":"An updated review of Parkinson's Disease genetics and clinicopathological correlations","volume":"135","author":"Ferreira","year":"2017","journal-title":"Acta Neurol Scand"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2562","DOI":"10.1111\/febs.17155","article-title":"A new mutation in the Parkinson's-related FBXO7 gene impairs mitochondrial and proteasomal function","volume":"291","author":"Navarro","year":"2024","journal-title":"FEBS J"},{"key":"B3","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/S1474-4422(19)30287-X","article-title":"The genetic architecture of Parkinson's Disease","volume":"19","author":"Blauwendraat","year":"2020","journal-title":"Lancet Neurol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1016\/j.ajhg.2008.05.005","article-title":"Genome-wide linkage analysis of a parkinsonian-pyramidal syndrome pedigree by 500\u2005K SNP arrays","volume":"82","author":"Shojaee","year":"2008","journal-title":"Am J Hum Genet"},{"key":"B5","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1212\/01.wnl.0000338144.10967.2b","article-title":"FBXO7 Mutations cause autosomal recessive, early-onset parkinsonian-pyramidal syndrome","volume":"20","author":"Fonzo","year":"2009","journal-title":"Neurology"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1791","DOI":"10.1002\/mds.23221","article-title":"Early-onset L-dopa-responsive parkinsonism with pyramidal signs due to ATP13A2, PLA2G6, FBXO7 and spatacsin mutations","volume":"25","author":"Pais\u00e1n-Ruiz","year":"2010","journal-title":"Mov Disord"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1016\/j.parkreldis.2014.06.024","article-title":"A new Turkish family with homozygous FBXO7 truncating mutation and juvenile atypical parkinsonism","volume":"20","author":"Yalcin-Cakmakli","year":"2014","journal-title":"Parkinsonism Relat Disord"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e23324","DOI":"10.1002\/jcla.23324","article-title":"Compound heterozygous variants of the FBXO7 gene resulting in infantile-onset parkinsonian-pyramidal syndrome in siblings of a Chinese family","volume":"34","author":"Jin","year":"2020","journal-title":"J Clin Lab Anal"},{"key":"B9","doi-asserted-by":"publisher","first-page":"2565","DOI":"10.1111\/febs.17114","article-title":"Study of an FBXO7 patient mutation reveals Fbxo7 and PI31 co-regulate proteasomes and mitochondria","volume":"291","author":"Al Rawi","year":"2024","journal-title":"FEBS J"},{"key":"B10","doi-asserted-by":"publisher","first-page":"146972","DOI":"10.1016\/j.gene.2022.146972","article-title":"The characteristics of FBXO7 and its role in human diseases","volume":"851","author":"Zhong","year":"2023","journal-title":"Gene"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e48911","DOI":"10.1371\/journal.pone.0048911","article-title":"Dopaminergic neuronal loss and dopamine-dependent locomotor defects in Fbxo7-deficient zebrafish","volume":"7","author":"Zhao","year":"2012","journal-title":"PLoS One"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2179","DOI":"10.1042\/BCJ20201000","article-title":"The parkinsonism-associated protein FBXO7 cooperates with the BAG6 complex in proteasome function and controls the subcellular localization of the complex","volume":"478","author":"Wang","year":"2021","journal-title":"Biochem J"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1016\/j.parkreldis.2014.07.016","article-title":"FBXO7-R498X Mutation: phenotypic variability from chorea to early onset parkinsonism within a family","volume":"20","author":"G\u00fcnd\u00fcz","year":"2014","journal-title":"Parkinsonism Relat Disord"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1002\/mds.26266","article-title":"A new F-box protein 7 gene mutation causing typical Parkinson's Disease","volume":"30","author":"Lohmann","year":"2015","journal-title":"Mov Disord"},{"key":"B15","doi-asserted-by":"publisher","first-page":"192e1","DOI":"10.1016\/j.neurobiolaging.2016.01.003","article-title":"FBXO7 Mutations in Parkinson's Disease and multiple system atrophy","volume":"40","author":"Conedera","year":"2016","journal-title":"Neurobiol Aging"},{"key":"B16","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.parkreldis.2017.11.332","article-title":"Juvenile-onset parkinsonism with pyramidal signs due to compound heterozygous mutations in the F-box only protein 7 gene","volume":"47","author":"Wei","year":"2018","journal-title":"Parkinsonism Relat Disord"},{"key":"B17","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.parkreldis.2020.09.035","article-title":"Novel compound heterozygous FBXO7 mutations in a family with early onset Parkinson's Disease","volume":"80","author":"Lorenzo-Betancor","year":"2020","journal-title":"Parkinsonism Relat Disord"},{"key":"B18","doi-asserted-by":"publisher","first-page":"225","DOI":"10.14802\/jmd.20026","article-title":"Young-Onset Parkinson's Disease with impulse control disorder due to novel variants of F-box only protein 7","volume":"13","author":"Yoo","year":"2020","journal-title":"J Mov Disord"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1002\/acn3.51095","article-title":"Impaired proteasome activity and neurodegeneration with brain iron accumulation in FBXO7 defect","volume":"7","author":"Correa-Vela","year":"2020","journal-title":"Ann Clin Transl Neurol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.parkreldis.2021.06.005","article-title":"A novel FBXO7-R345P mutation in a Chinese family with autosomal recessive parkinsonian-pyramidal syndrome","volume":"88","author":"Wang","year":"2021","journal-title":"Parkinsonism Relat Disord"},{"key":"B21","doi-asserted-by":"publisher","first-page":"269","DOI":"10.14802\/jmd.22006","article-title":"Nearly abolished dopamine transporter uptake in a patient with a novel FBXO7 mutation","volume":"15","author":"Kim","year":"2022","journal-title":"J Mov Disord"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1007\/s10072-023-07132-w","article-title":"Parkinsonism with prominent neuropsychiatric symptoms without pyramidal involvement in a patient with FBXO7 variants","volume":"45","author":"Mahajan","year":"2024","journal-title":"Neurol Sci"},{"key":"B23","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1186\/s13690-023-01112-4","article-title":"Whole genome sequencing diagnostic yield for paediatric patients with suspected genetic disorders: systematic review, meta-analysis, and GRADE assessment","volume":"81","author":"Nurchis","year":"2023","journal-title":"Arch Public Health"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1934625\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:31:07Z","timestamp":1789623067000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1934625\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":23,"alternative-id":["10.3389\/fped.2026.1934625"],"URL":"https:\/\/doi.org\/10.3389\/fped.2026.1934625","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]},"article-number":"1934625"}}