| H00420 | |
| H number | H00420 |
| Name | Familial partial lipodystrophy |
| Description | Familial partial lipodystrophy (FPL) is a rare autosomal dominant disorder characterized by variable loss of body fat from the extremities as well as from the truncal region. LMNA, PPARG and AKT2 have been identified in association with FPL. However, it is not yet known how these genes cause the disorder. Besides them, additional loci are likely as many FPL patients do not reveal any mutations in these genes. LMNA mutations may affect nuclear function, and may be involved in apoptosis and premature cell death of adipocytes, thus causing lipodystrophy. PPARG, PLIN1, and AKT2 are regulators of adipocyte differentiation. AKT2 is also involved in postreceptor insulin signaling. Thus, mutations in these three genes could result in lipodystrophy. The reason why loss of fat is restricted to partial areas remains unknown. Recently, novel autosomal recessive causes of partial lipodystrophy were reported. |
| Category | Inherited metabolic disorder |
| Network | nt06531(H00420) lipid and insulin related signaling |
| Gene | (FPLD2) LMNA [HSA:4000] [KO:K12641] (FPLD3) PPARG [HSA:5468] [KO:K08530] (FPLD4) PLIN1 [HSA:5346] [KO:K08768] (FPLD5) CIDEC [HSA:63924] [KO:K25878] (FPLD6) LIPE [HSA:3991] [KO:K07188] (FPLD7) CAV1 [HSA:857] [KO:K06278] (APLD) LMNB2 [HSA:84823] [KO:K07611] AKT2 [HSA:208] [KO:K04456] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | - |
| Comment | - |
| Other DBs | ICD-11: 5A44 ICD-10: E88.1 MeSH: D052496 OMIM: 608600 151660 604367 613877 615238 615980 608709 606721 |
| Reference | PMID:19494770 AUTHORS Simha V, Garg A TITLE Inherited lipodystrophies and hypertriglyceridemia. JOURNAL Curr Opin Lipidol 20:300-8 (2009) DOI:10.1097/MOL.0b013e32832d4a33 PMID:19162222 AUTHORS Garg A, Agarwal AK TITLE Lipodystrophies: disorders of adipose tissue biology. JOURNAL Biochim Biophys Acta 1791:507-13 (2009) DOI:10.1016/j.bbalip.2008.12.014 PMID:12074822 AUTHORS Bhayana S, Hegele RA TITLE The molecular basis of genetic lipodystrophies. JOURNAL Clin Biochem 35:171-7 (2002) DOI:10.1016/S0009-9120(02)00297-7 PMID:10587585 (LMNA) AUTHORS Cao H, Hegele RA TITLE Nuclear lamin A/C R482Q mutation in canadian kindreds with Dunnigan-type familial partial lipodystrophy. JOURNAL Hum Mol Genet 9:109-12 (2000) DOI:10.1093/hmg/9.1.109 PMID:10622252 (PPARG) AUTHORS Barroso I, Gurnell M, Crowley VE, Agostini M, Schwabe JW, Soos MA, Maslen GL, Williams TD, Lewis H, Schafer AJ, Chatterjee VK, O'Rahilly S TITLE Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension. JOURNAL Nature 402:880-3 (1999) DOI:10.1038/47254 PMID:21345103 (PLIN1) AUTHORS Gandotra S, Le Dour C, Bottomley W, Cervera P, Giral P, Reznik Y, Charpentier G, Auclair M, Delepine M, Barroso I, Semple RK, Lathrop M, Lascols O, Capeau J, O'Rahilly S, Magre J, Savage DB, Vigouroux C TITLE Perilipin deficiency and autosomal dominant partial lipodystrophy. JOURNAL N Engl J Med 364:740-8 (2011) DOI:10.1056/NEJMoa1007487 PMID:20049731 (CIDEC) AUTHORS Rubio-Cabezas O, Puri V, Murano I, Saudek V, Semple RK, Dash S, Hyden CS, Bottomley W, Vigouroux C, Magre J, Raymond-Barker P, Murgatroyd PR, Chawla A, Skepper JN, Chatterjee VK, Suliman S, Patch AM, Agarwal AK, Garg A, Barroso I, Cinti S, Czech MP, Argente J, O'Rahilly S, Savage DB TITLE Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC. JOURNAL EMBO Mol Med 1:280-7 (2009) DOI:10.1002/emmm.200900037 PMID:24848981 (LIPE) AUTHORS Albert JS, Yerges-Armstrong LM, Horenstein RB, Pollin TI, Sreenivasan UT, Chai S, Blaner WS, Snitker S, O'Connell JR, Gong DW, Breyer RJ 3rd, Ryan AS, McLenithan JC, Shuldiner AR, Sztalryd C, Damcott CM TITLE Null mutation in hormone-sensitive lipase gene and risk of type 2 diabetes. JOURNAL N Engl J Med 370:2307-2315 (2014) DOI:10.1056/NEJMoa1315496 PMID:18237401 (CAV1) AUTHORS Cao H, Alston L, Ruschman J, Hegele RA TITLE Heterozygous CAV1 frameshift mutations (MIM 601047) in patients with atypical partial lipodystrophy and hypertriglyceridemia. JOURNAL Lipids Health Dis 7:3 (2008) DOI:10.1186/1476-511X-7-3 PMID:16826530 (LMNB2) AUTHORS Hegele RA, Cao H, Liu DM, Costain GA, Charlton-Menys V, Rodger NW, Durrington PN TITLE Sequencing of the reannotated LMNB2 gene reveals novel mutations in patients with acquired partial lipodystrophy. JOURNAL Am J Hum Genet 79:383-9 (2006) DOI:10.1086/505885 PMID:19164855 (AKT2) AUTHORS Semple RK, Sleigh A, Murgatroyd PR, Adams CA, Bluck L, Jackson S, Vottero A, Kanabar D, Charlton-Menys V, Durrington P, Soos MA, Carpenter TA, Lomas DJ, Cochran EK, Gorden P, O'Rahilly S, Savage DB TITLE Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis. JOURNAL J Clin Invest 119:315-22 (2009) DOI:10.1172/JCI37432 |