{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T22:25:11Z","timestamp":1789943111013,"version":"4.0.1"},"reference-count":9,"publisher":"The Endocrine Society","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2000,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We previously identified a novel mutation, namely LMNA R482Q, that was found to underlie Dunnigan-type partial lipodystrophy (FPLD) and diabetes in an extended Canadian kindred. We have since sequenced LMNA in five additional Canadian FPLD probands and herein report three new rare missense mutations in LMNA: V440M, R482W, and R584H. One severely affected subject was a compound heterozygote for both V440M and R482Q. The findings indicated that 1) a spectrum of LMNA mutations underlies FPLD; 2) aberrant lamin A, and not lamin C, is likely to underlie FPLD, as R584H occurs within LMNA sequence that is specific for lamin A; 3) the V440M mutation may not cause lipodystrophy on its own; 4) compound heterozygosity for V440M and R482Q is associated with a relatively more severe FPLD phenotype, but not with complete lipodystrophy; and 5) variation in the severity of the phenotype might be related to environmental factors.<\/jats:p>","DOI":"10.1210\/jcem.85.9.6822","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:06:07Z","timestamp":1389200767000},"page":"3431-3435","source":"Crossref","is-referenced-by-count":6,"title":["Heterogeneity of Nuclear Lamin A Mutations in Dunnigan-Type Familial Partial Lipodystrophy*"],"prefix":"10.1210","volume":"85","author":[{"given":"Robert A.","family":"Hegele","sequence":"first","affiliation":[{"name":"Robarts Research Institute and Department of Medicine, University of Western Ontario, London, Ontario, Canada N6A 5K8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henian","family":"Cao","sequence":"additional","affiliation":[{"name":"Robarts Research Institute and Department of Medicine, University of Western Ontario, London, Ontario, Canada N6A 5K8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol M.","family":"Anderson","sequence":"additional","affiliation":[{"name":"Robarts Research Institute and Department of Medicine, University of Western Ontario, London, Ontario, Canada N6A 5K8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene M.","family":"Hramiak","sequence":"additional","affiliation":[{"name":"Robarts Research Institute and Department of Medicine, University of Western Ontario, London, Ontario, Canada N6A 5K8"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613474838900_R1","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1136\/jmg.23.2.120","article-title":"Familial partial lipodystrophy.","volume":"23","author":"Kobberling","year":"1986","journal-title":"J Med Genet"},{"key":"2020071613474838900_R2","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1136\/jmg.23.2.128","article-title":"Partial lipoatrophy with insulin resistant diabetes and hyperlipidemia (Dunnigan syndrome).","volume":"23","author":"Burn","year":"1986","journal-title":"J Med Genet"},{"key":"2020071613474838900_R3","first-page":"170","article-title":"Adipose tissue distribution pattern in patients with familial partial lipodystrophy (Dunnigan variety).","volume":"84","author":"Garg","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613474838900_R4","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1093\/hmg\/9.1.109","article-title":"Nuclear lamin A\/C R482Q mutation in Canadian kindreds with Dunnigan-type familial partial lipodystrophy.","volume":"9","author":"Cao","year":"2000","journal-title":"Hum Mol Genet"},{"key":"2020071613474838900_R5","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/6799","article-title":"Mutations in the gene encoding lamin A\/C cause autosomal dominant Emery-Dreifuss muscular dystrophy.","volume":"21","author":"Bonne","year":"1999","journal-title":"Nat Genet"},{"key":"2020071613474838900_R6","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1056\/NEJM199912023412302","article-title":"Missense mutations in the rod domain of the lamin A\/C gene as causes of dilated cardiomyopathy and conduction system disease.","volume":"341","author":"Fatkin","year":"1999","journal-title":"N Engl J Med"},{"key":"2020071613474838900_R7","doi-asserted-by":"crossref","first-page":"16321","DOI":"10.1016\/S0021-9258(19)85424-8","article-title":"Structural organization of the human gene encoding nuclear lamin A and nuclear lamin C.","volume":"268","author":"Lin","year":"1993","journal-title":"J Biol Chem"},{"key":"2020071613474838900_R8","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1006\/jsbi.1998.3987","article-title":"Nuclear lamins: their structure, assembly and interactions.","volume":"122","author":"Stuurman","year":"1998","journal-title":"J Struct Biol"},{"key":"2020071613474838900_R9","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/43448","article-title":"Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy.","volume":"401","author":"Shimomura","year":"1999","journal-title":"Nature"}],"container-title":["The Journal of Clinical Endocrinology &amp; 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