{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T07:11:44Z","timestamp":1794381104267,"version":"4.9.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"6","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,12,1]]},"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p><jats:italic>CAV1<\/jats:italic> encodes caveolin-1, a major protein of plasma membrane microdomains called caveolae, involved in several signaling pathways. Caveolin-1 is also located at the adipocyte lipid droplet. Heterozygous pathogenic variants of <jats:italic>CAV1<\/jats:italic> induce rare heterogeneous disorders including pulmonary arterial hypertension and neonatal progeroid syndrome. Only one patient was previously reported with a <jats:italic>CAV1<\/jats:italic> homozygous pathogenic variant, associated with congenital generalized lipodystrophy (CGL3). We aimed to further delineate genetic transmission, clinical, metabolic, and cellular characteristics of CGL3.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Design\/Methods<\/jats:title>\n<jats:p>In a large consanguineous kindred referred for CGL, we performed next-generation sequencing, as well as clinical, imagery, and metabolic investigations. We studied skin fibroblasts from the index case and the previously reported patient with CGL3.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Four patients, aged 8 months to 18 years, carried a new homozygous p.(His79Glnfs*3) <jats:italic>CAV1<\/jats:italic> variant. They all displayed generalized lipodystrophy since infancy, insulin resistance, low HDL-cholesterol, and\/or high triglycerides, but no pulmonary hypertension. Two patients also presented at the age of 15 and 18 years with dysphagia due to achalasia, and one patient had retinitis pigmentosa. Heterozygous parents and relatives (<jats:italic>n<\/jats:italic>\u2009= 9) were asymptomatic, without any metabolic abnormality. Patients\u2019 fibroblasts showed a complete loss of caveolae and no protein expression of caveolin-1 and its caveolin-2 and cavin-1 partners. Patients\u2019 fibroblasts also displayed insulin resistance, increased oxidative stress, and premature senescence.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>The<jats:italic> CAV1<\/jats:italic> null variant investigated herein leads to an autosomal recessive congenital lipodystrophy syndrome. Loss of caveolin-1 and\/or caveolae induces specific manifestations including achalasia which requires specific management. Overlapping phenotypic traits between the different <jats:italic>CAV1<\/jats:italic>-related diseases require further studies.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-21-0915","type":"journal-article","created":{"date-parts":[[2021,10,13]],"date-time":"2021-10-13T17:06:05Z","timestamp":1634144765000},"page":"841-854","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":29,"title":["Biallelic CAV1 null variants induce congenital generalized lipodystrophy with achalasia"],"prefix":"10.1093","volume":"185","author":[{"given":"Asuman Nur","family":"Karhan","sequence":"first","affiliation":[{"name":"1Department of Pediatric Gastroenterology, Hepatology and Nutrition, Mersin University Faculty of Medicine, Mersin, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamila","family":"Zammouri","sequence":"additional","affiliation":[{"name":"2Sorbonne University, Inserm UMR_S938, Saint-Antoine Research Centre, Institute of Cardiometabolism and Nutrition, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Auclair","sequence":"additional","affiliation":[{"name":"2Sorbonne University, Inserm UMR_S938, Saint-Antoine Research Centre, Institute of Cardiometabolism and Nutrition, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Capel","sequence":"additional","affiliation":[{"name":"2Sorbonne University, Inserm UMR_S938, Saint-Antoine Research Centre, Institute of Cardiometabolism and Nutrition, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feramuz Demir","family":"Apaydin","sequence":"additional","affiliation":[{"name":"3Department of Radiology, Mersin University Faculty of Medicine, Mersin, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fehmi","family":"Ates","sequence":"additional","affiliation":[{"name":"4Department of Gastroenterology, Mersin University Faculty of Medicine, Mersin, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Christine","family":"Verpont","sequence":"additional","affiliation":[{"name":"5Sorbonne University, Inserm UMR_S1155, LUMIC, Tenon Imagery and Cytometry Platform, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyne","family":"Magr\u00e9","sequence":"additional","affiliation":[{"name":"6Nantes University, CNRS, Inserm UMR_S1087, Institut du Thorax, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"F\u00e8ve","sequence":"additional","affiliation":[{"name":"2Sorbonne University, Inserm UMR_S938, Saint-Antoine Research Centre, Institute of Cardiometabolism and Nutrition, Paris, France"},{"name":"7Department of Endocrinology, Diabetology and Reproductive Endocrinology, Assistance Publique-H\u00f4pitaux de Paris, Saint-Antoine University Hospital, National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Lascols","sequence":"additional","affiliation":[{"name":"2Sorbonne University, Inserm UMR_S938, Saint-Antoine Research Centre, Institute of Cardiometabolism and Nutrition, Paris, France"},{"name":"8Department of Molecular Biology and Genetics, Assistance Publique-H\u00f4pitaux de Paris, Saint-Antoine University Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuf","family":"Usta","sequence":"additional","affiliation":[{"name":"1Department of Pediatric Gastroenterology, Hepatology and Nutrition, Mersin University Faculty of Medicine, Mersin, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"J\u00e9ru","sequence":"additional","affiliation":[{"name":"2Sorbonne University, Inserm UMR_S938, Saint-Antoine Research Centre, Institute of Cardiometabolism and Nutrition, Paris, France"},{"name":"8Department of Molecular Biology and Genetics, Assistance Publique-H\u00f4pitaux de Paris, Saint-Antoine University Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Vigouroux","sequence":"additional","affiliation":[{"name":"2Sorbonne University, Inserm UMR_S938, Saint-Antoine Research Centre, Institute of Cardiometabolism and Nutrition, Paris, France"},{"name":"7Department of Endocrinology, Diabetology and Reproductive Endocrinology, Assistance Publique-H\u00f4pitaux de Paris, Saint-Antoine University Hospital, National Reference Center for Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS), Paris, France"},{"name":"8Department of Molecular Biology and Genetics, Assistance Publique-H\u00f4pitaux de Paris, Saint-Antoine University Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/185\/6\/EJE-21-0915.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/downloadpdf\/journals\/eje\/185\/6\/EJE-21-0915.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:17:21Z","timestamp":1676391441000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/185\/6\/841\/6654317"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,1]]},"references-count":0,"journal-issue":{"issue":"6"},"URL":"https:\/\/doi.org\/10.1530\/eje-21-0915","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,1]]}}}