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Uniquely, certain variants in BSCL2 can cause both generalized congenital lipodystrophy type 2, upper and\/or lower motor neuron diseases, or progressive encephalopathy, with a poor prognosis during childhood. The latter, Celia\u2019s encephalopathy, which may or may not be associated with generalized lipodystrophy, is caused by the c.985C &gt;T variant. This cytosine to thymine transition creates a cryptic splicing zone that leads to intronization of exon 7, resulting in an aberrant form of seipin, Celia seipin. It has been proposed that the accumulation of this protein, both in the endoplasmic reticulum and in the nucleus of neurons, might be the pathogenetic mechanism of this neurodegenerative condition. In recent years, other variants in BSCL2 associated with generalized lipodystrophy and progressive epileptic encephalopathy have been reported. Interestingly, most of these variants could also lead to the loss of exon 7. In this review, we analyzed the molecular bases of Celia\u2019s encephalopathy and its pathogenic mechanisms, the clinical features of the different variants, and a therapeutic approach in order to slow down the progression of this fatal neurological disorder.<\/jats:p>","DOI":"10.3390\/jcm10071435","type":"journal-article","created":{"date-parts":[[2021,4,1]],"date-time":"2021-04-01T07:23:17Z","timestamp":1617261797000},"page":"1435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Celia\u2019s Encephalopathy (BSCL2-Gene-Related): Current Understanding"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3887-0573","authenticated-orcid":false,"given":"Sof\u00eda","family":"S\u00e1nchez-Iglesias","sequence":"first","affiliation":[{"name":"UETeM-Molecular Pathology Group, Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS-CIMUS, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1268-7538","authenticated-orcid":false,"given":"Ant\u00eda","family":"Fern\u00e1ndez-Pombo","sequence":"additional","affiliation":[{"name":"UETeM-Molecular Pathology Group, Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS-CIMUS, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"},{"name":"Division of Endocrinology and Nutrition, University Clinical Hospital of Santiago de Compostela, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0941-626X","authenticated-orcid":false,"given":"Silvia","family":"Cobelo-G\u00f3mez","sequence":"additional","affiliation":[{"name":"UETeM-Molecular Pathology Group, Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS-CIMUS, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3757-262X","authenticated-orcid":false,"given":"\u00c1lvaro","family":"Hermida-Ameijeiras","sequence":"additional","affiliation":[{"name":"UETeM-Molecular Pathology Group, Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS-CIMUS, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"},{"name":"Division of Internal Medicine, University Clinical Hospital of Santiago de Compostela, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Alarc\u00f3n-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Hospital Virgen de la Arrixaca and IMIB-Arrixaca, CIBERER-ISCIII, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosario","family":"Domingo-Jim\u00e9nez","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Hospital Virgen de la Arrixaca and IMIB-Arrixaca, CIBERER-ISCIII, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6581-7132","authenticated-orcid":false,"given":"Alejandro Iv\u00e1n","family":"Ru\u00edz Riquelme","sequence":"additional","affiliation":[{"name":"German Center for Neurodegenerative Diseases (DZNE), 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas R.","family":"Requena","sequence":"additional","affiliation":[{"name":"Prion Laboratory, CIMUS Biomedical Research Institute, University of Santiago de Compostela-IDIS, Santiago de Compostela, 15782 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ara\u00fajo-Vilar","sequence":"additional","affiliation":[{"name":"UETeM-Molecular Pathology Group, Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS-CIMUS, University of Santiago de Compostela, 15782 Santiago de Compostela, Spain"},{"name":"Division of Endocrinology and Nutrition, University Clinical Hospital of Santiago de Compostela, 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1136\/jmedgenet-2013-101525","article-title":"A new seipin-associated neurodegenerative syndrome","volume":"50","author":"Victoria","year":"2013","journal-title":"J. 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