{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:24:19Z","timestamp":1790688259443,"version":"4.1.0"},"reference-count":41,"publisher":"American Society for Clinical Investigation","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,6,16]]},"abstract":"<jats:p>\n                    Despite identification of causal genes for various lipodystrophy syndromes, the molecular basis of some peculiar lipodystrophies remains obscure. In an African-American pedigree with a novel autosomal dominant, atypical familial partial lipodystrophy (FPLD), we performed linkage analysis for candidate regions and whole-exome sequencing to identify the disease-causing mutation. Affected adults reported marked loss of fat from the extremities, with excess fat in the face and neck at age 13\u201315 years, and developed metabolic complications later. A heterozygous g.112837956C&gt;T mutation on chromosome 10 (c.202C&gt;T, p.Leu68Phe) affecting a highly conserved residue in adrenoceptor \u03b1 2A (\n                    <jats:italic>ADRA2A<\/jats:italic>\n                    ) was found in all affected subjects but not in unaffected relatives. ADRA2A is the main presynaptic inhibitory feedback G protein\u2013coupled receptor regulating norepinephrine release. Activation of ADRA2A inhibits cAMP production and reduces lipolysis in adipocytes. As compared with overexpression of a wild-type ADRA2A construct in human embryonic kidney\u2013293 cells and differentiated 3T3-L1 adipocytes, the mutant ADRA2A produced more cAMP and glycerol, which were resistant to the effects of the \u03b12-adrenergic receptor agonist clonidine and the \u03b12-adrenergic receptor antagonist yohimbine, suggesting loss of function. We conclude that heterozygous p.Leu68Phe ADRA2A mutation causes a rare atypical FPLD, most likely by inducing excessive lipolysis in some adipose tissue depots.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.86870","type":"journal-article","created":{"date-parts":[[2016,6,15]],"date-time":"2016-06-15T14:17:40Z","timestamp":1466000260000},"source":"Crossref","is-referenced-by-count":34,"title":["Whole-exome sequencing identifies ADRA2A mutation in atypical familial partial lipodystrophy"],"prefix":"10.1172","volume":"1","author":[{"given":"Abhimanyu","family":"Garg","sequence":"first","affiliation":[{"name":"Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, and Center for Human Nutrition,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shireesha","family":"Sankella","sequence":"additional","affiliation":[{"name":"Division of Nutrition and Metabolic Diseases, Department of Internal Medicine, and Center for Human 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