{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:49:12Z","timestamp":1791978552761,"version":"4.4.0"},"reference-count":33,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T00:00:00Z","timestamp":1603324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Cerebral folate deficiency (CFD) is a neurological disorder characterized by low levels of 5-methyltetrahydrofolate (5-MTHF) in the cerebrospinal fluid (CSF). The prevalence of this autosomal recessive disorder is estimated to be &lt;1\/1,000,000. Fifteen different pathogenic variants in the folate receptor 1 gene (FOLR1) encoding the receptor of folate \u03b1 (FR\u03b1) have already been described. We present a new pathogenic variation in the FOLR1 in a childhood-stage patient. We aim to establish the core structure of the FR\u03b1 protein mandatory for its activity. A three-year-old child was admitted at hospital for a first febrile convulsions episode. Recurrent seizures without fever also occurred a few months later, associated with motor and cognitive impairment. Various antiepileptic drugs failed to control seizures. Magnetic resonance imaging (MRI) showed central hypomyelination and biological analysis revealed markedly low levels of 5-MTHF in CSF. Next generation sequencing (NGS) confirmed a CFD with a FOLR1 homozygous variation (c.197 G &gt; A, p.Cys66Tyr). This variation induces an altered folate receptor \u03b1 protein and underlines the role of a disulfide bond: Cys66-Cys109, essential to transport 5-MTHF into the central nervous system. Fortunately, this severe form of CFD had remarkably responded to high doses of oral folinic acid combined with intravenous administrations.<\/jats:p>","DOI":"10.3390\/brainsci10110762","type":"journal-article","created":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T10:27:58Z","timestamp":1603362478000},"page":"762","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Pharmacoresistant Epilepsy in Childhood: Think of the Cerebral Folate Deficiency, a Treatable Disease"],"prefix":"10.3390","volume":"10","author":[{"given":"Sarah","family":"Mafi","sequence":"first","affiliation":[{"name":"CHU de Limoges, Service de Biochimie et G\u00e9n\u00e9tique Mol\u00e9culaire, F-87000 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Laroche-Raynaud","sequence":"additional","affiliation":[{"name":"CHU de Limoges, Service de P\u00e9diatrie, F-87000 Limoges, France"},{"name":"CHU de Limoges, Centre de Comp\u00e9tence des Maladies H\u00e9r\u00e9ditaires du M\u00e9tabolisme, F-87000 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Chazelas","sequence":"additional","affiliation":[{"name":"CHU de Limoges, Service de Biochimie et G\u00e9n\u00e9tique Mol\u00e9culaire, F-87000 Limoges, France"},{"name":"Facult\u00e9 de M\u00e9decine, EA6309 Maintenance My\u00e9linique et Neuropathies P\u00e9riph\u00e9riques, Universit\u00e9 de Limoges, F-87000 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6509-1578","authenticated-orcid":false,"given":"Anne-Sophie","family":"Lia","sequence":"additional","affiliation":[{"name":"CHU de Limoges, Service de Biochimie et G\u00e9n\u00e9tique Mol\u00e9culaire, F-87000 Limoges, France"},{"name":"Facult\u00e9 de M\u00e9decine, EA6309 Maintenance My\u00e9linique et Neuropathies P\u00e9riph\u00e9riques, Universit\u00e9 de Limoges, F-87000 Limoges, France"},{"name":"CHU Limoges, UF de Bioinformatique, F-87000 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paco","family":"Derouault","sequence":"additional","affiliation":[{"name":"CHU Limoges, UF de Bioinformatique, F-87000 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6428-5162","authenticated-orcid":false,"given":"Franck","family":"Sturtz","sequence":"additional","affiliation":[{"name":"CHU de Limoges, Service de Biochimie et G\u00e9n\u00e9tique Mol\u00e9culaire, F-87000 Limoges, France"},{"name":"Facult\u00e9 de M\u00e9decine, EA6309 Maintenance My\u00e9linique et Neuropathies P\u00e9riph\u00e9riques, Universit\u00e9 de Limoges, F-87000 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasser","family":"Baaj","sequence":"additional","affiliation":[{"name":"CHU de Limoges, Service de Biochimie et G\u00e9n\u00e9tique Mol\u00e9culaire, F-87000 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Froget","sequence":"additional","affiliation":[{"name":"CHU de Limoges, Service de P\u00e9diatrie, F-87000 Limoges, France"},{"name":"CHU Limoges, INSERM CIC 1435, F-87000 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marl\u00e8ne","family":"Rio","sequence":"additional","affiliation":[{"name":"CHU Necker, Enfants Malades, Paris, APHP, Service de G\u00e9n\u00e9tique, F-75743 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Fran\u00e7ois","family":"Benoist","sequence":"additional","affiliation":[{"name":"CHU Necker, Enfants Malades, Paris, APHP, Service de Biochimie M\u00e9tabolomique, F-75743 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4453-187X","authenticated-orcid":false,"given":"Fran\u00e7ois","family":"Poumeaud","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine, EA6309 Maintenance My\u00e9linique et Neuropathies P\u00e9riph\u00e9riques, Universit\u00e9 de Limoges, F-87000 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3754-0070","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Favreau","sequence":"additional","affiliation":[{"name":"CHU de Limoges, Service de Biochimie et G\u00e9n\u00e9tique Mol\u00e9culaire, F-87000 Limoges, France"},{"name":"Facult\u00e9 de M\u00e9decine, EA6309 Maintenance My\u00e9linique et Neuropathies P\u00e9riph\u00e9riques, Universit\u00e9 de Limoges, F-87000 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9291-3795","authenticated-orcid":false,"given":"Pierre-Antoine","family":"Faye","sequence":"additional","affiliation":[{"name":"CHU de Limoges, Service de Biochimie et G\u00e9n\u00e9tique Mol\u00e9culaire, F-87000 Limoges, France"},{"name":"Facult\u00e9 de M\u00e9decine, EA6309 Maintenance My\u00e9linique et Neuropathies P\u00e9riph\u00e9riques, Universit\u00e9 de Limoges, F-87000 Limoges, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2022","DOI":"10.1093\/brain\/aws122","article-title":"Molecular characterization of folate receptor 1 mutations delineates cerebral folate transport 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