KEGG DISEASE: Familial partial lipodystrophy

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

Inherited metabolic disorder

Brite

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

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]
(FPLD8) ADRA2A [HSA:150] [KO:K04138]
(FPLD9) PLAAT3 [HSA:11145] [KO:K16817]
(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 606721 620679 620683 608709

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

Reference

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

Reference

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

Reference

PMID:10587585 (FPLD2)

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 (FPLD3)

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 (FPLD4)

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 (FPLD5)

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 (FPLD6)

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 (FPLD7)

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:27376152 (FPLD8)

Authors

Garg A, Sankella S, Xing C, Agarwal AK

Title

Whole-exome sequencing identifies ADRA2A mutation in atypical familial partial lipodystrophy.

Journal

JCI Insight 1:e86870 (2016)
DOI:10.1172/jci.insight.86870

Reference

PMID:37919452 (FPLD9)

Authors

Schuermans N, El Chehadeh S, Hemelsoet D, Gautheron J, Vantyghem MC, Nouioua S, Tazir M, Vigouroux C, Auclair M, Bogaert E, Dufour S, Okawa F, Hilbert P, Van Doninck N, Taquet MC, Rosseel T, De Clercq G, Debackere E, Van Haverbeke C, Cherif FR, Urtizberea JA, Chanson JB, Funalot B, Authier FJ, Kaya S, Terryn W, Callens S, Depypere B, Van Dorpe J, Poppe B, Impens F, Mizushima N, Depienne C, Jeru I, Dermaut B

Title

Loss of phospholipase PLAAT3 causes a mixed lipodystrophic and neurological syndrome due to impaired PPARgamma signaling.

Journal

Nat Genet 55:1929-1940 (2023)
DOI:10.1038/s41588-023-01535-3

Reference

PMID:16826530 (APLD)

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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Disease (10)   
   OMIM (10)   
Gene (20)   
   KEGG ORTHOLOGY (10)   
   KEGG GENES (10)   
Literature (13)   
   PubMed (13)   
All databases (43)   

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