{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T05:12:38Z","timestamp":1771305158986,"version":"3.50.1"},"reference-count":10,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,7,7]],"date-time":"2017-07-07T00:00:00Z","timestamp":1499385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01\u2010DK105448"],"award-info":[{"award-number":["R01\u2010DK105448"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR001105"],"award-info":[{"award-number":["UL1 TR001105"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec><jats:label\/><jats:p>The <jats:italic>LMNA<\/jats:italic> gene contains 12 exons and encodes lamins A and C by alternative splicing within exon 10. While mutations in lamin A specific residues cause several diseases including lipodystrophy, progeria, muscular dystrophy, neuropathy, and cardiomyopathy, only three families with mutations in lamin C\u2010specific residues are reported with cardiomyopathy, neuropathy, and muscular dystrophy so far. We now report two brothers with juvenile\u2010onset generalized lipodystrophy due to a lamin C\u2010specific mutation. The proband, a 23\u2010year\u2010old Caucasian male was reported to have generalized lipodystrophy at 3 weeks of age, developed diabetes, hypertriglyceridemia, hypertension and liver problems and died with complications of cirrhosis, and kidney failure. His younger brother, a 37\u2010year\u2010old Caucasian male developed generalized lipodystrophy around 2 years of age and was diagnosed with diabetes, hypertriglyceridemia, fatty liver, and hypertension at 36 years of age. Their father also died of end stage renal disease at age 52 years. Exome sequencing of the proband revealed an extremely rare missense heterozygous variant c.1711_1712CG&gt;TC; p.(Arg571Ser) in <jats:italic>LMNA<\/jats:italic> which was confirmed by Sanger sequencing in both the patients. Interestingly, the mutation had no effect on mRNA splicing or relative expression of lamin A or C mRNA and protein in the lymphoblasts. Our observations suggest that mutant lamin C disrupts its interaction with other cellular proteins resulting in generalized lipodystrophy due to defective development and maintenance of adipose tissue.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38341","type":"journal-article","created":{"date-parts":[[2017,7,7]],"date-time":"2017-07-07T14:24:41Z","timestamp":1499437481000},"page":"2517-2521","source":"Crossref","is-referenced-by-count":19,"title":["Juvenile\u2010onset generalized lipodystrophy due to a novel heterozygous missense <i>LMNA<\/i> mutation affecting lamin C"],"prefix":"10.1002","volume":"173","author":[{"given":"Nivedita","family":"Patni","sequence":"first","affiliation":[{"name":"Division of Pediatric Endocrinology Department of Pediatrics Center for Human Nutrition UT Southwestern Medical Center Dallas Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Xing","sequence":"additional","affiliation":[{"name":"McDermott Center for Human Growth and Development and Departments of Bioinformatics and Clinical Sciences UT Southwestern Medical Center Dallas Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anil K.","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Division of Nutrition and Metabolic Diseases Department of Internal Medicine and the Center for Human Nutrition UT Southwestern Medical Center Dallas Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7209-6986","authenticated-orcid":false,"given":"Abhimanyu","family":"Garg","sequence":"additional","affiliation":[{"name":"Division of Nutrition and Metabolic Diseases Department of Internal Medicine and the Center for Human Nutrition UT Southwestern Medical Center Dallas Texas"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,7,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2003-030855"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2004.046110"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199912023412302"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1550"},{"issue":"1","key":"e_1_2_8_6_1","first-page":"161","article-title":"Generalized equations for predicting body density of men. 1978","volume":"91","author":"Jackson A. 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