Inherited and acquired lipodystrophies: molecular-genetic and autoimmune mechanisms

Abstract


Lipodystrophy syndromes form a heterogenous group of inherited or acquired rare disorders, characterized by total (generalized lipodystrophy) or partial fat loss (partial lipodystrophy), usually accompanied by different metabolic disorders. Based on etiology lipodystrophies can be inherited or acquired. As a result of a significant progress in molecular genetics 20 new genes, associated with different lipodystrophy syndromes, were discovered during the last 20 years. However according to the majority of researchers’ data mutations in these causative genes are not found in approximately half of the patients. This might mean the need for both further molecular-genetic studies and the search for autoimmune factors playing a role in lipodystrophy syndromes etiology.


Ekaterina L Sorkina

Author for correspondence.
sorkina@bk.ru
ORCID iD: 0000-0001-7006-0664
SPIN-code: 7777-0248
Endocrinology research centre, Moscow, Russia
Russian Federation, 117036, Moscow, ulitsa Dmitriya Ulyanova, 11

research assistant of clamp-technologies laboratory

Anatoly Tiulpakov

anatolytiulpakov@gmail.com
SPIN-code: 8396-1798
Endocrinology research centre, Moscow, Russia
Russian Federation, 117036, Moscow, ulitsa Dmitriya Ulyanova, 11

Sc.D., head of the department of inherited endocrine disorders

  • Chiquette E, Oral E, Garg A, et al. Estimating the prevalence of generalized and partial lipodystrophy: findings and challenges. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 2017;Volume 10:375-383. doi: 10.2147/dmso.s130810.
  • Brown RJ, Araujo-Vilar D, Cheung PT, et al. The Diagnosis and Management of Lipodystrophy Syndromes: A Multi-Society Practice Guideline. J. Clin. Endocr. Metab. 2016;101(12):4500-4511. doi: 10.1210/jc.2016-2466.
  • Agarwal AK, Garg A. A Novel Heterozygous Mutation in Peroxisome Proliferator-Activated Receptor-γ Gene in a Patient with Familial Partial Lipodystrophy. J. Clin. Endocr. Metab. 2002;87(1):408-408. doi: 10.1210/jcem.87.1.8290.
  • Magré J, Delépine M, Khallouf E, et al. Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13. Nat. Genet. 2001;28(4):365-370. doi: 10.1038/ng585.
  • Garg A, Kircher M, del Campo M, et al. Whole exome sequencing identifies de novo heterozygousCAV1mutations associated with a novel neonatal onset lipodystrophy syndrome. Am. J. Med. Genet. A. 2015;167(8):1796-1806. doi: 10.1002/ajmg.a.37115.
  • Kim CA, Delépine M, Boutet E, et al. Association of a Homozygous Nonsense Caveolin-1 Mutation with Berardinelli-Seip Congenital Lipodystrophy. J. Clin. Endocr. Metab. 2008;93(4):1129-1134. doi: 10.1210/jc.2007-1328.
  • Hayashi YK, Matsuda C, Ogawa M, et al. Human PTRF mutations cause secondary deficiency of caveolins resulting in muscular dystrophy with generalized lipodystrophy. J. Clin. Invest. 2009;119(9):2623-2633. doi: 10.1172/jci38660.
  • Barsh GS, Rajab A, Straub V, et al. Fatal Cardiac Arrhythmia and Long-QT Syndrome in a New Form of Congenital Generalized Lipodystrophy with Muscle Rippling (CGL4) Due to PTRF-CAVIN Mutations. PLoS Genet.2010;6(3):e1000874. doi: 10.1371/journal.pgen.1000874.
  • Shastry S, Delgado MR, Dirik E, et al. Congenital generalized lipodystrophy, type 4 (CGL4) associated with myopathy due to novel PTRF mutations. Am. J. Med. Genet. A. 2010;152A(9):2245-2253. doi: 10.1002/ajmg.a.33578.
  • Herbst KL, Tannock LR, Deeb SS, et al. Kobberling Type of Familial Partial Lipodystrophy: An underrecognized syndrome. Diabetes Care. 2003;26(6):1819-1824. doi: 10.2337/diacare.26.6.1819.
  • Shackleton S, Lloyd DJ, Jackson SNJ, et al. LMNA, encoding lamin A/C, is mutated in partial lipodystrophy. Nat. Genet. 2000;24(2):153-156. doi: 10.1038/72807.
  • Barroso I, Gurnell M, Crowley VEF, et al. Dominant negative mutations in human PPARγ associated with severe insulin resistance, diabetes mellitus and hypertension. Nature. 1999;402(6764):880-883. doi: 10.1038/47254.
  • Gandotra S, Le Dour C, Bottomley W, et al. Perilipin Deficiency and Autosomal Dominant Partial Lipodystrophy. N. Engl. J. Med. 2011;364(8):740-748. doi: 10.1056/NEJMoa1007487.
  • Rubio-Cabezas O, Puri V, Murano I, et al. Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation inCIDEC. EMBO Mol. Med. 2009;1(5):280-287. doi: 10.1002/emmm.200900037.
  • Farhan SMK, Robinson JF, McIntyre AD, et al. A Novel LIPE Nonsense Mutation Found Using Exome Sequencing in Siblings With Late-Onset Familial Partial Lipodystrophy. Can. J. Cardiol. 2014;30(12):1649-1654. doi: 10.1016/j.cjca.2014.09.007.
  • Albert JS, Yerges-Armstrong LM, Horenstein RB, et al. Null Mutation in Hormone-Sensitive Lipase Gene and Risk of Type 2 Diabetes. N. Engl. J. Med. 2014;370(24):2307-2315. doi: 10.1056/NEJMoa1315496.
  • Semple RK, Sleigh A, Murgatroyd PR, et al. Postreceptor insulin resistance contributes to human dyslipidemia and hepatic steatosis. J. Clin. Invest. 2009. doi: 10.1172/jci37432.
  • De Sandre-Giovannoli A, Bernard R, Cau P, et al. Lamin a truncation in Hutchinson-Gilford progeria. Science. 2003;300(5628):2055-2055.
  • Donadille B, D’Anella P, Auclair M, et al. Partial lipodystrophy with severe insulin resistance and adult progeria Werner syndrome. Orphanet J. Rare Dis. 2013;8(1):106. doi: 10.1186/1750-1172-8-106.
  • Yu CE, Oshima J, Fu YH, et al. Positional Cloning of the Werner’s Syndrome Gene. Science. 1996;272(5259):258-262. doi: 10.1126/science.272.5259.258.
  • Goto M, Tanimoto K, Horiuchi Y, Sasazuki T. Family analysis of Werner’s syndrome: A survey of 42 Japanese families with a review of the literature. Clin. Genet. 2008;19(1):8-15. doi: 10.1111/j.1399-0004.1981.tb00660.x.
  • Chen W, Zhou H, Saha P, et al. Molecular Mechanisms Underlying Fasting Modulated Liver Insulin Sensitivity and Metabolism in Male LipodystrophicBscl2/Seipin-Deficient Mice. Endocrinology. 2014;155(11):4215-4225. doi: 10.1210/en.2014-1292.
  • Csoka AB. Novel lamin A/C gene (LMNA) mutations in atypical progeroid syndromes. J. Med. Genet.2004;41(4):304-308. doi: 10.1136/jmg.2003.015651.
  • Hussain I, Patni N, Ueda M, et al. A Novel Generalized Lipodystrophy-Associated Progeroid Syndrome Due to Recurrent Heterozygous LMNA p.T10I Mutation. J. Clin. Endocr. Metab. 2018;103(3):1005-1014. doi: 10.1210/jc.2017-02078.
  • Novelli G, Muchir A, Sangiuolo F, et al. Mandibuloacral Dysplasia Is Caused by a Mutation in LMNA-Encoding Lamin A/C. The American Journal of Human Genetics. 2002;71(2):426-431. doi: 10.1086/341908.
  • Agarwal AK, Simha V, Oral EA, et al. Phenotypic and Genetic Heterogeneity in Congenital Generalized Lipodystrophy. J. Clin. Endocr. Metab. 2003;88(10):4840-4847. doi: 10.1210/jc.2003-030855.
  • Simha V, Agarwal AK, Oral EA, et al. Genetic and Phenotypic Heterogeneity in Patients with Mandibuloacral Dysplasia-Associated Lipodystrophy. J. Clin. Endocr. Metab. 2003;88(6):2821-2824. doi: 10.1210/jc.2002-021575.
  • Weedon MN, Ellard S, Prindle MJ, et al. An in-frame deletion at the polymerase active site of POLD1 causes a multisystem disorder with lipodystrophy. Nat. Genet. 2013;45(8):947-950. doi: 10.1038/ng.2670.
  • Lessel D, Vaz B, Halder S, et al. Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic instability and progeroid features. Nat. Genet. 2014;46(11):1239-1244. doi: 10.1038/ng.3103.
  • Cabanillas R, Cadiñanos J, Villameytide JAF, et al. Néstor-Guillermo progeria syndrome: A novel premature aging condition with early onset and chronic development caused by BANF1 mutations. Am. J. Med. Genet. A. 2011;155(11):2617-2625. doi: 10.1002/ajmg.a.34249.
  • Graul-Neumann LM, Kienitz T, Robinson PN, et al. Marfan syndrome with neonatal progeroid syndrome-like lipodystrophy associated with a novel frameshift mutation at the 3' terminus of the FBN1-gene. Am. J. Med. Genet. A. 2010;152A(11):2749-2755. doi: 10.1002/ajmg.a.33690.
  • Masotti A, Uva P, Davis-Keppen L, et al. Keppen-Lubinsky Syndrome Is Caused by Mutations in the Inwardly Rectifying K+ Channel Encoded by KCNJ6. The American Journal of Human Genetics. 2015;96(2):295-300. doi: 10.1016/j.ajhg.2014.12.011.
  • Agarwal AK, Xing C, DeMartino GN, et al. PSMB8 Encoding the β5i Proteasome Subunit Is Mutated in Joint Contractures, Muscle Atrophy, Microcytic Anemia, and Panniculitis-Induced Lipodystrophy Syndrome. The American Journal of Human Genetics. 2010;87(6):866-872. doi: 10.1016/j.ajhg.2010.10.031.
  • Savage DB, Semple RK, Clatworthy MR, et al. Complement Abnormalities in Acquired Lipodystrophy Revisited. J. Clin. Endocr. Metab. 2009;94(1):10-16. doi: 10.1210/jc.2008-1703.
  • Hegele RA, Cao H, Liu DM, et al. Sequencing of the Reannotated LMNB2 Gene Reveals Novel Mutations in Patients with Acquired Partial Lipodystrophy. The American Journal of Human Genetics. 2006;79(2):383-389. doi: 10.1086/505885.
  • Lupsa BC, Sachdev V, Lungu AO, et al. Cardiomyopathy in Congenital and Acquired Generalized Lipodystrophy. Medicine. 2010;89(4):245-250. doi: 10.1097/MD.0b013e3181e9442f.

Views

Abstract - 182

PDF (Russian) - 86


Copyright (c) 2018 Sorkina E.L., Tiulpakov A.

Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.