H00420 | |
H番号 | H00420 |
名称 | 家族性部分型リポジストロフィー |
概要 | 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. |
カテゴリ | 先天性代謝異常症 |
ネットワーク | nt06531(H00420) lipid and insulin related signaling |
病因遺伝子 | (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] |
病原体 | - |
環境要因 | - |
発癌物質 | - |
治療薬 | - |
コメント | - |
リンク | ICD-11: 5A44 ICD-10: E88.1 MeSH: D052496 OMIM: 608600 151660 604367 613877 615238 615980 608709 606721 |
文献 | PMID:19494770 著者 Simha V, Garg A タイトル Inherited lipodystrophies and hypertriglyceridemia. 雑誌 Curr Opin Lipidol 20:300-8 (2009) DOI:10.1097/MOL.0b013e32832d4a33 PMID:19162222 著者 Garg A, Agarwal AK タイトル Lipodystrophies: disorders of adipose tissue biology. 雑誌 Biochim Biophys Acta 1791:507-13 (2009) DOI:10.1016/j.bbalip.2008.12.014 PMID:12074822 著者 Bhayana S, Hegele RA タイトル The molecular basis of genetic lipodystrophies. 雑誌 Clin Biochem 35:171-7 (2002) DOI:10.1016/S0009-9120(02)00297-7 PMID:10587585 (LMNA) 著者 Cao H, Hegele RA タイトル Nuclear lamin A/C R482Q mutation in canadian kindreds with Dunnigan-type familial partial lipodystrophy. 雑誌 Hum Mol Genet 9:109-12 (2000) DOI:10.1093/hmg/9.1.109 PMID:10622252 (PPARG) 著者 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 タイトル Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension. 雑誌 Nature 402:880-3 (1999) DOI:10.1038/47254 PMID:21345103 (PLIN1) 著者 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 タイトル Perilipin deficiency and autosomal dominant partial lipodystrophy. 雑誌 N Engl J Med 364:740-8 (2011) DOI:10.1056/NEJMoa1007487 PMID:20049731 (CIDEC) 著者 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 タイトル Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC. 雑誌 EMBO Mol Med 1:280-7 (2009) DOI:10.1002/emmm.200900037 PMID:24848981 (LIPE) 著者 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 タイトル Null mutation in hormone-sensitive lipase gene and risk of type 2 diabetes. 雑誌 N Engl J Med 370:2307-2315 (2014) DOI:10.1056/NEJMoa1315496 PMID:18237401 (CAV1) 著者 Cao H, Alston L, Ruschman J, Hegele RA タイトル Heterozygous CAV1 frameshift mutations (MIM 601047) in patients with atypical partial lipodystrophy and hypertriglyceridemia. 雑誌 Lipids Health Dis 7:3 (2008) DOI:10.1186/1476-511X-7-3 PMID:16826530 (LMNB2) 著者 Hegele RA, Cao H, Liu DM, Costain GA, Charlton-Menys V, Rodger NW, Durrington PN タイトル Sequencing of the reannotated LMNB2 gene reveals novel mutations in patients with acquired partial lipodystrophy. 雑誌 Am J Hum Genet 79:383-9 (2006) DOI:10.1086/505885 PMID:19164855 (AKT2) 著者 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 タイトル Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis. 雑誌 J Clin Invest 119:315-22 (2009) DOI:10.1172/JCI37432 |