{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:05:58Z","timestamp":1791515158503,"version":"4.3.4"},"reference-count":10,"publisher":"The Endocrine Society","issue":"12","funder":[{"name":"French Ministry of Solidarity and Health and","award":["CRMR PRISIS"],"award-info":[{"award-number":["CRMR PRISIS"]}]},{"DOI":"10.13039\/501100009820","name":"Assistance publique-H\u00f4pitaux de Paris","doi-asserted-by":"publisher","award":["PRISIS"],"award-info":[{"award-number":["PRISIS"]}],"id":[{"id":"10.13039\/501100009820","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sorbonne Universit\u00e9","award":["CRSA"],"award-info":[{"award-number":["CRSA"]}]},{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","award":["ANR-10-IAIHU-05"],"award-info":[{"award-number":["ANR-10-IAIHU-05"]}],"id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT 107064"],"award-info":[{"award-number":["WT 107064"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MRC_MC_UU_12012.1"],"award-info":[{"award-number":["MRC_MC_UU_12012.1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"name":"French Ministry of Health","award":["PHRC 2009"],"award-info":[{"award-number":["PHRC 2009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Heterozygous frameshift variants in PLIN1 encoding perilipin-1, a key protein for lipid droplet formation and triglyceride metabolism, have been implicated in familial partial lipodystrophy type 4 (FPLD4), a rare entity with only six families reported worldwide. The pathogenicity of other PLIN1 null variants identified in patients with diabetes and\/or hyperinsulinemia was recently questioned because of the absence of lipodystrophy in these individuals and the elevated frequency of PLIN1 null variants in the general population.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To reevaluate the pathogenicity of PLIN1 frameshift variants owing to new data obtained in the largest series of patients with FPLD4.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We performed histological and molecular studies for patients referred to our French National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity for lipodystrophy and\/or insulin resistance and carrying PLIN1 frameshift variants.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We identified two heterozygous PLIN1 frameshift variants segregating with the phenotype in nine patients from four unrelated families. The FPLD4 stereotypical signs included postpubertal partial lipoatrophy of variable severity, muscular hypertrophy, acromegaloid features, polycystic ovary syndrome and\/or hirsutism, metabolic complications (e.g., hypertriglyceridemia, liver steatosis, insulin resistance, diabetes), and disorganized subcutaneous fat lobules with fibrosis and macrophage infiltration.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These data suggest that some FPLD4-associated PLIN1 variants are deleterious. Thus, the evidence for the pathogenicity of each variant ought to be carefully considered before genetic counseling, especially given the importance of an early diagnosis for optimal disease management. Thus, we recommend detailed familial investigation, adipose tissue-focused examination, and follow-up of metabolic evolution.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jc.2019-00849","type":"journal-article","created":{"date-parts":[[2019,6,27]],"date-time":"2019-06-27T09:00:37Z","timestamp":1561626037000},"page":"6025-6032","source":"Crossref","is-referenced-by-count":42,"title":["Diagnostic Challenge in PLIN1-Associated Familial Partial Lipodystrophy"],"prefix":"10.1210","volume":"104","author":[{"given":"Isabelle","family":"J\u00e9ru","sequence":"first","affiliation":[{"name":"Sorbonne University, Inserm U938, Saint-Antoine Research Centre and Institute of CardioMetabolism and Nutrition, Paris, France"},{"name":"Department of Molecular Biology and Genetics, Assistance Publique-H\u00f4pitaux de Paris, Saint-Antoine University Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Christine","family":"Vantyghem","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetology and Metabolism, Lille University Hospital, Lille, France"},{"name":"Inserm U1190, European Genomic Institute for Diabetes, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Bismuth","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology and Diabetology, Competence Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity, Paris-Diderot University, Sorbonne Paris Cit\u00e9, Assistance Publique-H\u00f4pitaux de Paris, Robert Debr\u00e9 University Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Cervera","sequence":"additional","affiliation":[{"name":"Department of Pathology, Sorbonne University, Inserm U938, Assistance Publique-H\u00f4pitaux de Paris, Saint-Antoine University Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Barraud","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes, Nutrition, Reims University Hospital, Reims, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"PLIN1-Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Auclair","sequence":"additional","affiliation":[{"name":"Sorbonne University, Inserm U938, Saint-Antoine Research Centre and Institute of CardioMetabolism and Nutrition, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Vatier","sequence":"additional","affiliation":[{"name":"Sorbonne University, Inserm U938, Saint-Antoine Research Centre and Institute of CardioMetabolism and Nutrition, Paris, France"},{"name":"Department of Endocrinology, Diabetology and Reproductive Endocrinology, National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity, Assistance Publique Hopitaux de Paris, Saint Antoine University Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Lascols","sequence":"additional","affiliation":[{"name":"Sorbonne University, Inserm U938, Saint-Antoine Research Centre and Institute of CardioMetabolism and Nutrition, Paris, France"},{"name":"Department of Molecular Biology and Genetics, Assistance Publique-H\u00f4pitaux de Paris, Saint-Antoine University Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B","family":"Savage","sequence":"additional","affiliation":[{"name":"Metabolic Research Libraries, University of Cambridge, Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8181-4721","authenticated-orcid":false,"given":"Corinne","family":"Vigouroux","sequence":"additional","affiliation":[{"name":"Sorbonne University, Inserm U938, Saint-Antoine Research Centre and Institute of CardioMetabolism and Nutrition, Paris, France"},{"name":"Department of Molecular Biology and Genetics, Assistance Publique-H\u00f4pitaux de Paris, Saint-Antoine University Hospital, Paris, France"},{"name":"Department of Endocrinology, Diabetology and Reproductive Endocrinology, National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity, Assistance Publique Hopitaux de Paris, Saint Antoine University Hospital, Paris, 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