KEGG   DISEASE: Familial partial lipodystrophy
Entry
H00420                      Disease                                
Name
Familial partial lipodystrophy
  Subgroup
Kobberling-type lipodystrophy (FPLD1)
Dunnigan-type lipodystrophy (FPLD2)
Dunnigan-like lipodystrophy (FPLD3)
Acquired partial lipodystrophy (APLD)
AKT2 associated lipodystrophy
  Supergrp
Lipodystrophy [DS:H01475]
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
Congenital disorder of metabolism
Brite
Human diseases [BR:br08402]
 Congenital disorders of metabolism
  Other congenital disorders of metabolism
   H00420  Familial partial lipodystrophy
Human diseases in ICD-11 classification [BR:br08403]
 05 Endocrine, nutritional or metabolic diseases
  Endocrine diseases
   Other disorders of glucose regulation or pancreatic internal secretion
    5A44  Insulin-resistance syndromes
     H00420  Familial partial lipodystrophy
Related
pathway
hsa04210  Apoptosis
hsa04371  Apelin signaling pathway
hsa04152  AMPK signaling pathway
hsa04923  Regulation of lipolysis in adipocytes
hsa03320  PPAR signaling pathway
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]
Other DBs
ICD-11: 5A44
ICD-10: E88.1
MeSH: D052496
OMIM: 608600 151660 604367 613877 615238 615980 608709 606721
Reference
  Authors
Simha V, Garg A
  Title
Inherited lipodystrophies and hypertriglyceridemia.
  Journal
Curr Opin Lipidol 20:300-8 (2009)
DOI:10.1097/MOL.0b013e32832d4a33
Reference
  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
Reference
  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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
Reference
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
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