{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:00:12Z","timestamp":1760058012098,"version":"build-2065373602"},"reference-count":14,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,8]],"date-time":"2025-03-08T00:00:00Z","timestamp":1741392000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive disorder characterized by extreme hypertriglyceridemia (&gt;1000 mg\/dL), recurrent pancreatitis, and lipoprotein lipase (LPL) deficiency. Mutations in the LMF1 gene, encoding a chaperone protein required for LPL maturation, can lead to combined lipase deficiency. This study reports a case of a 33-year-old Ecuadorian mestizo woman presenting with recurrent pancreatitis secondary to severe hypertriglyceridemia, in whom two LMF1 variants of uncertain significance (VUS) were identified. Methods: Whole-exome sequencing (WES) was performed on the patient and her asymptomatic son using next-generation sequencing (NGS). Data analysis included computational pathogenicity predictors (REVEL, PolyPhen, SIFT, MutationTaster, etc.). Two LMF1 variants\u2014c.1142C&gt;T (p.Pro381Leu) and c.897G&gt;A (p.Gln299Gln)\u2014were identified. Their pathogenic potential was assessed based on allele frequency (gnomAD), bioinformatics predictions, and ACMG criteria. Results: Both variants were classified as VUS, with c.897G&gt;A predicted to affect splicing, potentially leading to loss of function. The c.1142C&gt;T (p.Pro381Leu) variant, despite its low frequency, remains unclassified due to insufficient evidence. The patient\u2019s son carried one variant but was asymptomatic. The patient\u2019s phenotype suggested an intermediate form between monogenic and polygenic hypertriglyceridemia. Conclusions: This is a new Ecuadorian report of LMF1-related hypertriglyceridemia, highlighting the need for functional studies to confirm pathogenicity. Given the classification of both variants as VUS, further research is required to elucidate their clinical significance. This case underscores the necessity of a combined genetic and biochemical approach for diagnosing and managing severe hypertriglyceridemia.<\/jats:p>","DOI":"10.3390\/jcm14061827","type":"journal-article","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T05:46:52Z","timestamp":1741585612000},"page":"1827","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of a Pathogenic Mutation of the Lipase Maturation Factor 1 (LMF1) Gene Causing Recurrent Pancreatitis and Requiring Critical Care"],"prefix":"10.3390","volume":"14","author":[{"given":"Andr\u00e9s Fernando","family":"Montalvo","sequence":"first","affiliation":[{"name":"Hospital Provincial Pablo Arturo Suarez, \u00c1ngel Lude\u00f1a y Machala Oe5261, Quito 170301, Ecuador"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2091-9095","authenticated-orcid":false,"given":"Fabricio","family":"Gonz\u00e1lez-Andrade","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud, Direcci\u00f3n de Posgrados, Universidad Tecnol\u00f3gica Indoam\u00e9rica, Calle Machala y Sabanilla, Quito 170301, Ecuador"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Molestina","sequence":"additional","affiliation":[{"name":"Hospital Provincial Pablo Arturo Suarez, \u00c1ngel Lude\u00f1a y Machala Oe5261, Quito 170301, Ecuador"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jhonny Manuel","family":"Carranza","sequence":"additional","affiliation":[{"name":"Hospital Provincial Pablo Arturo Suarez, \u00c1ngel Lude\u00f1a y Machala Oe5261, Quito 170301, Ecuador"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Maldonado","sequence":"additional","affiliation":[{"name":"SYNLAB-Ecuador, Calle Oe7A N31-145 y Av. Mariana de Jes\u00fas, Quito 170129, Ecuador"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6895-6442","authenticated-orcid":false,"given":"Denise","family":"Battaglini","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences and Integrated Diagnostics, University of Genova, 16126 Genova, Italy"},{"name":"Anesthesia and Intensive Care, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6956-4475","authenticated-orcid":false,"given":"Jorge Luis","family":"V\u00e9lez-Pa\u00e9z","sequence":"additional","affiliation":[{"name":"Hospital Provincial Pablo Arturo Suarez, \u00c1ngel Lude\u00f1a y Machala Oe5261, Quito 170301, Ecuador"},{"name":"Facultad de Ciencias M\u00e9dicas, Unidad de Medicina Traslacional, Universidad Central del Ecuador, Iquique N14-121 y Sodiro-Itchimb\u00eda, Quito 170403, Ecuador"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alves, M., Laranjeira, F., and Correia-da-Silva, G. (2024). Understanding Hypertriglyceridemia: Integrating Genetic Insights. Genes, 15.","DOI":"10.3390\/genes15020190"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s12944-022-01631-z","article-title":"Causes, clinical findings and therapeutic options in chylomicronemia syndrome, a special form of hypertriglyceridemia","volume":"21","author":"Paragh","year":"2022","journal-title":"Lipids Health Dis."},{"key":"ref_3","first-page":"56","article-title":"Familial chylomicronemia and multifactorial chylomicronemia. Quilomicronemia familiar y quilomicronemia multifactorial","volume":"33","year":"2021","journal-title":"Clin. Investig. Arterioscler."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Dron, J.S., and Hegele, R.A. (2020). Genetics of Hypertriglyceridemia. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.00455"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.tem.2024.02.016","article-title":"A unified model for regulating lipoprotein lipase activity","volume":"35","author":"Zhang","year":"2024","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.jacl.2018.10.006","article-title":"Severe hypertriglyceridemia is primarily polygenic","volume":"13","author":"Dron","year":"2019","journal-title":"J. Clin. Lipidol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"626","DOI":"10.7326\/M19-0203","article-title":"The Chylomicronemia Syndrome Is Most Often Multifactorial: A Narrative Review of Causes and Treatment","volume":"170","author":"Chait","year":"2019","journal-title":"Ann. Intern. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.jacl.2020.01.003","article-title":"The polygenic nature of mild-to-moderate hypertriglyceridemia","volume":"14","author":"Dron","year":"2020","journal-title":"J. Clin. Lipidol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"814295","DOI":"10.3389\/fgene.2022.814295","article-title":"A Heterozygous LMF1 Gene Mutation (c.1523C>T), Combined With an LPL Gene Mutation (c.590G>A), Aggravates the Clinical Symptoms in Hypertriglyceridemia","volume":"13","author":"Guo","year":"2022","journal-title":"Front. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1016\/j.bbalip.2011.10.006","article-title":"Lipase maturation factor 1: A lipase chaperone involved in lipid metabolism","volume":"1821","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"20503121241289828","DOI":"10.1177\/20503121241289828","article-title":"The role of lipase maturation factor 1 in hypertriglyceridaemia and atherosclerosis: An update","volume":"12","author":"Dabravolski","year":"2024","journal-title":"SAGE Open Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.atherosclerosissup.2016.10.002","article-title":"Diagnostic algorithm for familial chylomicronemia syndrome","volume":"23","author":"Stroes","year":"2017","journal-title":"Atheroscler. Suppl."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.jacl.2022.02.006","article-title":"Severe hypertriglyceridemia secondary to splice-site and missense variants in LMF1 in three patients from Ecuador","volume":"16","author":"Gaete","year":"2022","journal-title":"J. Clin. Lipidol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/6\/1827\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:49:25Z","timestamp":1760028565000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/6\/1827"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,8]]},"references-count":14,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["jcm14061827"],"URL":"https:\/\/doi.org\/10.3390\/jcm14061827","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2025,3,8]]}}}