LMNA基因突变相关脂肪萎缩综合征的研究进展

doi:10.16288/j.yczz.22-225

遗传 ›› 2022, Vol. 44 ›› Issue (10): 913-925.doi: 10.16288/j.yczz.22-225

LMNA基因突变相关脂肪萎缩综合征的研究进展

肖诚¹(), 刘洁颖^1,², 杨春如¹, 于淼¹()

1. 中国医学科学院北京协和医学院,北京协和医院内分泌科,国家卫生健康委员会内分泌重点实验室,北京 100730
2. 中国医学科学院北京协和医学院,北京协和医院医学科学研究中心,疑难重症及罕见病国家重点实验室,北京 100730

收稿日期:2022-06-30 修回日期:2022-09-06 出版日期:2022-10-20 发布日期:2022-09-20
通讯作者: 于淼 E-mail:jz_xiaocheng@163.com;yumiaoxh@163.com
作者简介:肖诚,在读博士研究生,专业方向：内分泌与代谢病方向。E-mail: jz_xiaocheng@163.com
基金资助:
国家自然科学基金项目(82170855);科技部国家重点研发计划项目(2020YFC2004505);科技部国家重点研发计划项目(2018YFC2001105)

Advances in lipodystrophy syndrome caused by LMNA gene mutation

Cheng Xiao¹(), Jieying Liu^1,², Chunru Yang¹, Miao Yu¹()

1. Department of Endocrinology, Key Laboratory of Endocrinology, National Health Commission, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China
2. Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China

Received:2022-06-30 Revised:2022-09-06 Online:2022-10-20 Published:2022-09-20
Contact: Yu Miao E-mail:jz_xiaocheng@163.com;yumiaoxh@163.com
Supported by:
the National Nature Science Foundation of China(82170855);the National Key Research and Development Program(2020YFC2004505);the National Key Research and Development Program(2018YFC2001105)

摘要/Abstract

摘要：

LMNA基因突变相关脂肪萎缩综合征(lipodystrophy syndrome)是一组由A型核纤层蛋白(lamin A/C, LMNA)基因突变引起的常染色体显性遗传单基因疾病,以选择性脂肪缺失伴胰岛素抵抗等代谢异常为特征。本文总结了目前已报道的可引起脂肪萎缩综合征的LMNA突变位点,及该突变位点导致的代谢并发症、心血管异常、性腺轴紊乱、肌病、肾脏异常等多种临床表现,阐述了LMNA基因致病性突变位点可能的致病机制及诊疗方法,以期为该疾病的基础研究和临床诊治提供参考。

关键词: 脂肪萎缩综合征, LMNA基因突变, 胰岛素抵抗, 代谢紊乱性疾病, 致病机制

Abstract:

Lipodystrophy syndrome caused by LMNA gene mutation is a group of autosomal dominant monogenic diseases, characterized by selective fat loss and metabolic abnormalities with insulin resistance. In this review, we summarize the clinical manifestations caused by multiple pathogenic LMNA mutations reported so far, including metabolic complications, cardiovascular abnormalities, gonadal axis disorders, myopathy, and renal abnormalities. Meanwhile, we also clarify the possible pathogenic mechanism, diagnosis, and treatment, in order to improve the understanding of the disease and to provide a reference for basic research and clinical diagnosis and treatment of this disease.

Key words: lipodystrophy syndrome, LMNA gene mutation, insulin resistance, metabolic disorders, pathogenic mechanisms

肖诚, 刘洁颖, 杨春如, 于淼. LMNA基因突变相关脂肪萎缩综合征的研究进展[J]. 遗传, 2022, 44(10): 913-925.

Cheng Xiao, Jieying Liu, Chunru Yang, Miao Yu. Advances in lipodystrophy syndrome caused by LMNA gene mutation[J]. Hereditas(Beijing), 2022, 44(10): 913-925.

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参考文献 96

[1]	Garg A. Clinical review#: lipodystrophies: genetic and acquired body fat disorders. J Clin Endocrinol Metab, 2011, 96(11): 3313-3325. doi: 10.1210/jc.2011-1159 pmid: 21865368
[2]	Garg A. Lipodystrophies. Am J Med, 2000, 108(2): 143-152. pmid: 11126308
[3]	Mann JP, Savage DB. What lipodystrophies teach us about the metabolic syndrome. J Clin Invest, 2019, 129(10): 4009-4021.
[4]	Brown RJ, Araujo-Vilar D, Cheung PT, Dunger D, Garg A, Jack M, Mungai L, Oral EA, Patni N, Rother KI, von Schnurbein J, Sorkina E, Stanley T, Vigouroux C, Wabitsch M, Williams R, Yorifuji T, The diagnosis and management of lipodystrophy syndromes: a multi-society practice guideline. J Clin Endocrinol Metab, 2016, 101(12): 4500-4511. doi: 10.1210/jc.2016-2466 pmid: 27710244
[5]	Schreiber KH, Kennedy BK. When lamins go bad: nuclear structure and disease. Cell, 2013, 152(6): 1365-1375. doi: 10.1016/j.cell.2013.02.015 pmid: 23498943
[6]	Osmanagic-Myers S, Foisner R. The structural and gene expression hypotheses in laminopathic diseases-not so different after all. Mol Biol Cell, 2019, 30(15): 1786-1790. doi: 10.1091/mbc.E18-10-0672 pmid: 31306095
[7]	Sekizkardes H, Cochran E, Malandrino N, Garg A, Brown RJ. Efficacy of metreleptin treatment in familial partial lipodystrophy due to PPARG vs LMNA pathogenic variants. J Clin Endocrinol Metab, 2019, 104(8): 3068- 3076. doi: 10.1210/jc.2018-02787 pmid: 31194872
[8]	Diker-Cohen T, Cochran E, Gorden P, Brown RJ. Partial and generalized lipodystrophy: comparison of baseline characteristics and response to metreleptin. J Clin Endocrinol Metab, 2015, 100(5): 1802-1810. doi: 10.1210/jc.2014-4491 pmid: 25734254
[9]	Bertrand AT, Chikhaoui K, Yaou RB, Bonne G. Clinical and genetic heterogeneity in laminopathies. Biochem Soc Trans, 2011, 39(6): 1687-1692. doi: 10.1042/BST20110670
[10]	Subramanyam L, Simha V, Garg A. Overlapping syndrome with familial partial lipodystrophy, Dunnigan variety and cardiomyopathy due to amino-terminal heterozygous missense lamin A/C mutations. Clin Genet, 2010, 78(1): 66-73. doi: 10.1111/j.1399-0004.2009.01350.x pmid: 20041886
[11]	Strelkov SV, Schumacher J, Burkhard P, Aebi U, Herrmann H. Crystal structure of the human lamin A coil 2B dimer: implications for the head-to-tail association of nuclear lamins. J Mol Biol, 2004, 343(4): 1067-1080. pmid: 15476822
[12]	Mory PB, Crispim F, Kasamatsu T, Gabbay MA, Dib SA, Moisés RS. Atypical generalized lipoatrophy and severe insulin resistance due to a heterozygous LMNA p.T10I mutation. Arq Bras Endocrinol Metabol, 2008, 52(8): 1252-1256. doi: 10.1590/S0004-27302008000800008
[13]	Jiajue R, Feng K, Wang R, Xia W. Recurrent femoral fractures in a boy with an atypical progeroid syndrome: a case report. Calcif Tissue Int, 2020, 106(3): 325-330. doi: 10.1007/s00223-019-00639-5
[14]	Fukaishi T, Minami I, Masuda S, Miyachi Y, Tsujimoto K, Izumiyama H, Hashimoto K, Yoshida M, Takahashi S, Kashimada K, Morio T, Kosaki K, Maezawa Y, Yokote K, Yoshimoto T, Yamada T. A case of generalized lipodystrophy-associated progeroid syndrome treated by leptin replacement with short and long-term monitoring of the metabolic and endocrine profiles. Endocr J, 2020, 67(2): 211-218. doi: 10.1507/endocrj.EJ19-0226 pmid: 31708526
[15]	Sahinoz M, Khairi S, Cuttitta A, Brady GF, Rupani A, Meral R, Tayeh MK, Thomas P, Riebschleger M, Camelo-Piragua S, Innis JW, Bishr Omary M, Michele DE, Oral EA. Potential association of LMNA-associated generalized lipodystrophy with juvenile dermatomyositis. Clin Diabetes Endocrinol, 2018, 4: 6. doi: 10.1186/s40842-018-0058-3 pmid: 29610677
[16]	Hussain I, Patni N, Ueda M, Sorkina E, Valerio CM, Cochran E, Brown RJ, Peeden J, Tikhonovich Y, Tiulpakov A, Stender SRS, Klouda E, Tayeh MK, Innis JW, Meyer A, Lal P, Godoy-Matos AF, Teles MG, Adams-Huet B, Rader DJ, Hegele RA, Oral EA, Garg A. A novel generalized lipodystrophy-associated progeroid syndrome due to recurrent heterozygous LMNA p.T10I mutation. J Clin Endocrinol Metab, 2018, 103(3): 1005-1014. doi: 10.1210/jc.2017-02078 pmid: 29267953
[17]	Cardona-Hernández R, Suárez-Ortega L, Torres M. Difficult to manage diabetes mellitus associated with generalized congenital lipodystrophy. Report of two cases. An Pediatr (Barc), 2011, 74(2): 126-130.
[18]	Csoka AB, Cao H, Sammak PJ, Constantinescu D, Schatten GP, Hegele RA. Novel lamin A/C gene (LMNA) mutations in atypical progeroid syndromes. J Med Genet, 2004, 41(4): 304-308. pmid: 15060110
[19]	Garg A, Speckman RA, Bowcock AM. Multisystem dystrophy syndrome due to novel missense mutations in the amino-terminal head and alpha-helical rod domains of the lamin A/C gene. Am J Med, 2002, 112(7): 549-555. pmid: 12015247
[20]	Decaudain A, Vantyghem MC, Guerci B, Hécart AC, Auclair M, Reznik Y, Narbonne H, Ducluzeau PH, Donadille B, Lebbé C, Béréziat V, Capeau J, Lascols O, Vigouroux C. New metabolic phenotypes in laminopathies: LMNA mutations in patients with severe metabolic syndrome. J Clin Endocrinol Metab, 2007, 92(12): 4835-4844. doi: 10.1210/jc.2007-0654
[21]	Türk M, Wehnert M, Schröder R, Chevessier F., Multisystem disorder and limb girdle muscular dystrophy caused by LMNA p.R28W mutation. Neuromuscul Disord, 2013, 23(7): 587-590. doi: 10.1016/j.nmd.2013.04.008
[22]	Ambonville C, Bouldouyre MA, Laforêt P, Richard P, Benveniste O, Vigouroux C. A complex case of diabetes due to LMNA mutation. Rev Med Interne, 2017, 38(10): 695-699. doi: S0248-8663(17)30471-X pmid: 28545855
[23]	Kutbay NO, Yurekli BS, Onay H, Altay CT, Atik T, Hekimsoy Z, Saygili F, Akinci B. A case of familial partial lipodystrophy caused by a novel lamin A/C (LMNA) mutation in exon 1 (D47N). Eur J Intern Med, 2016, 29: 37-39. doi: 10.1016/j.ejim.2015.12.012 pmid: 26775134
[24]	Akinci B, Onay H, Demir T, Savas-Erdeve Ş, Gen R, Simsir IY, Keskin FE, Erturk MS, Uzum AK, Yaylali GF, Ozdemir NK, Atik T, Ozen S, Yurekli BS, Apaydin T, Altay C, Akinci G, Demir L, Comlekci A, Secil M, Oral EA. Clinical presentations, metabolic abnormalities and end-organ complications in patients with familial partial lipodystrophy. Metabolism, 2017, 72: 109-119. doi: 10.1016/j.metabol.2017.04.010
[25]	van der Kooi AJ, Bonne G, Eymard B, Duboc D, Talim B, Van der Valk M, Reiss P, Richard P, Demay L, Merlini L, Schwartz K, Busch HF, Lamin A/C mutations with lipodystrophy, cardiac abnormalities, and muscular dystrophy. Neurology, 2002, 59(4): 620-623. pmid: 12196663
[26]	Fatkin D, MacRae C, Sasaki T, Wolff MR, Porcu M, Frenneaux M, Atherton J, Vidaillet Jr HJ, Spudich S, De Girolami U, Seidman JG, Seidman C, Muntoni F, Müehle G, Johnson W, McDonough B. Missense mutations in the rod domain of the lamin A/C gene as causes of dilated cardiomyopathy and conduction-system disease. N Engl J Med, 1999, 341(23): 1715-1724. doi: 10.1056/NEJM199912023412302
[27]	He GY, Yan Z, Sun L, Lv Y, Guo W, Gang XK, Wang G. Diabetes mellitus coexisted with progeria: a case report of atypical Werner syndrome with novel LMNA mutations and literature review. Endocr J, 2019, 66(11): 961-969.
[28]	Cecchetti C, D'Apice MR, Morini E, Novelli G, Pizzi C, Pagotto U, Gambineri A. Case report:an atypical form of familial partial lipodystrophy type 2 due to mutation in the rod domain of lamin A/C. Front Endocrinol (Lausanne), 2021, 12: 675096.
[29]	Lanktree M, Cao H, Rabkin SW, Hanna A, Hegele RA., Novel LMNA mutations seen in patients with familial partial lipodystrophy subtype 2 (FPLD2; MIM 151660). Clin Genet, 2007, 71(2): 183-186. pmid: 17250669
[30]	Araújo-Vilar D, Victoria B, González-Méndez B, Barreiro F, Fernández-Rodríguez B, Cereijo R, Gallego-Escuredo JM, Villarroya F, Pañeda-Menéndez A. Histological and molecular features of lipomatous and nonlipomatous adipose tissue in familial partial lipodystrophy caused by LMNA mutations. Clin Endocrinol (Oxf), 2012, 76(6): 816-824. doi: 10.1111/j.1365-2265.2011.04208.x
[31]	Mahdi L, Kahn A, Dhamija R, Vargas HE. Hepatic steatosis resulting from LMNA-associated familial lipodystrophy. ACG Case Rep J, 2020, 7(4): e00375. doi: 10.14309/crj.0000000000000375
[32]	Motegi S, Yokoyama Y, Uchiyama A, Ogino S, Takeuchi Y, Yamada K, Hattori T, Hashizume H, Ishikawa Y, Goto M, Ishikawa O., First Japanese case of atypical progeroid syndrome/atypical Werner syndrome with heterozygous LMNA mutation. J Dermatol, 2014, 41(12): 1047-1052. doi: 10.1111/1346-8138.12657
[33]	Renard D, Fourcade G, Milhaud D, Bessis D, Esteves-Vieira V, Boyer A, Roll P, Bourgeois P, Levy N, De Sandre-Giovannoli A. Novel LMNA mutation in atypical Werner syndrome presenting with ischemic disease. Stroke, 2009, 40(2): e11-e14.
[34]	Mory PB, Crispim F, Freire MB, Salles JE, Valério CM, Godoy-Matos AF, Dib SA, Moisés RS. Phenotypic diversity in patients with lipodystrophy associated with LMNA mutations. Eur J Endocrinol, 2012, 167(3): 423-431. doi: 10.1530/EJE-12-0268
[35]	Jeru I, Vatier C, Vantyghem MC, Lascols O, Vigouroux C. LMNA-associated partial lipodystrophy: anticipation of metabolic complications. J Med Genet, 2017, 54(6): 413-416. doi: 10.1136/jmedgenet-2016-104437 pmid: 28408391
[36]	van Tintelen JP, Hofstra RM, Katerberg H, Rossenbacker T, Wiesfeld ACP, du Marchie Sarvaas GJ, Wilde AAM, van Langen IM, Nannenberg EA, van der Kooi AJ, Kraak M, van Gelder IC, van Veldhuisen DJ, Vos Y, van den Berg MP,Working Group on Inherited Cardiac Disorders,line 27/50, Interuniversity Cardiology Institute of The Netherlands. High yield of LMNA mutations in patients with dilated cardiomyopathy and/or conduction disease referred to cardiogenetics outpatient clinics. Am Heart J, 2007. 154(6): 1130-1139. pmid: 18035086
[37]	Fountas A, Giotaki Z, Dounousi E, Liapis G, Bargiota A, Tsatsoulis A, Tigas S. Familial partial lipodystrophy and proteinuric renal disease due to a missense c.1045C > T LMNA mutation. Endocrinol Diabetes Metab Case Rep, 2017, 2017: 0017-0049.
[38]	Andre P, Schneebeli S, Vigouroux C, Lascols O, Schaaf M, Chevalier P. Metabolic and cardiac phenotype characterization in 37 atypical Dunnigan patients with nonfarnesylated mutated prelamin A. Am Heart J, 2015, 169(4): 587-593. doi: 10.1016/j.ahj.2014.12.021 pmid: 25819867
[39]	Muschke P, Kölsch U, Jakubiczka S, Wieland I, Brune T, Wieacker P. The heterozygous LMNA mutation p.R471G causes a variable phenotype with features of two types of familial partial lipodystrophy. Am J Med Genet A, 2007, 143A(23): 2810-2814. pmid: 18041775
[40]	Saha B, Lessel D, Hisama FM, Leistritz DF, Friedrich K, Martin GM, Kubisch C, Oshima J. A novel LMNA mutation causes altered nuclear morphology and symptoms of familial partial lipodystrophy (Dunnigan variety) with progeroid features. Mol Syndromol, 2010, 1(3): 127-132. doi: 10.1159/000320166 pmid: 21031082
[41]	Wehnert MS, Feuer A, Wasner C, Hoeltzenbein M. Novel P485R mutation in LMNA presenting with features of a progeroid syndrome. Neuromuscular Disorders, 2004, 14: 591-592.
[42]	Adiyaman SC, Yuksel BD, Ferrari CT, Eldin AJ, Saydam BO, Altay C, Sharma P, Bhave N, Little A, McKeever P, Onay H, Ozkal S, Secil M, Yenerel MN, Akinci B, Oral EA. Unusual presentations of LMNA- associated lipodystrophy with complex phenotypes and generalized fat loss: when the genetic diagnosis uncovers novel features. AACE Clin Case Rep, 2020, 6(2): e79-e85.
[43]	Morel CF, Thomas MA, Cao H, O'Neil CH, Pickering JG, Foulkes WD, Hegele RA. A LMNA splicing mutation in two sisters with severe Dunnigan-type familial partial lipodystrophy type 2. J Clin Endocrinol Metab, 2006, 91(7): 2689-2695. doi: 10.1210/jc.2005-2746
[44]	Chirico V, FerraùV, Loddo I, Briuglia S, Amorini M, Salpietro V, Lacquaniti A, Salpietro C, Arrigo T. LMNA gene mutation as a model of cardiometabolic dysfunction: from genetic analysis to treatment response. Diabetes Metab, 2014, 40(3): 224-228. doi: 10.1016/j.diabet.2013.12.008 pmid: 24485160
[45]	Savage DB, Soos MA, Powlson A, O'Rahilly S, McFarlane I, Halsall DJ, Barroso I, Thomas EL, Bell JD, Scobie I, Belchetz PE, Kelly WF, Schafer AJ. Familial partial lipodystrophy associated with compound heterozygosity for novel mutations in the LMNA gene. Diabetologia, 2004, 47(4): 753-756.
[46]	Chan D, McIntyre AD, Hegele RA, Don-Wauchope AC. Familial partial lipodystrophy presenting as metabolic syndrome. J Clin Lipidol, 2016, 10(6): 1488-1491. doi: S1933-2874(16)30302-6 pmid: 27919367
[47]	Guillín-Amarelle C, Sánchez-Iglesias S, Mera A, Pintos E, Castro-Pais A, Rodríguez-Cañete L, Pardo J, Casanueva FF, Araújo-Vilar D. Inflammatory myopathy in the context of an unusual overlapping laminopathy. Arch Endocrinol Metab, 2018, 62(3): 376-382. doi: S2359-39972018000300376 pmid: 29791652
[48]	Patni N, Hatab S, Xing C, Zhou Z, Quittner C, Garg A. A novel autosomal recessive lipodystrophy syndrome due to homozygous LMNA variant. J Med Genet, 2020, 57(6): 422-426. doi: 10.1136/jmedgenet-2019-106395
[49]	Patni N, Xing C, Agarwal AK, Garg A. Juvenile-onset generalized lipodystrophy due to a novel heterozygous missense LMNA mutation affecting lamin C. Am J Med Genet A, 2017, 173(9): 2517-2521. doi: 10.1002/ajmg.a.38341
[50]	Montenegro Jr RM, Costa-Riquetto AD, Fernandes VO, Montenegro A, de Santana LS, Jorge AAL, Karbage L, Aguiar LB, Carvalho FHC, Teles MG, d'Alva CB. Homozygous and heterozygous nuclear lamin A p.R582C mutation: different lipodystrophic phenotypes in the same kindred. Front Endocrinol (Lausanne), 2018, 9: 458. doi: 10.3389/fendo.2018.00458
[51]	Kao KT, Zacharin M. An adolescent girl referred with Cushing syndrome—does she or does she not have the syndrome? J Pediatr Endocrinol Metab, 2016, 29(1): 109-112.
[52]	Garg A, Vinaitheerthan M, Weatherall PT, Bowcock AM. Phenotypic heterogeneity in patients with familial partial lipodystrophy (dunnigan variety) related to the site of missense mutations in lamin a/c gene. J Clin Endocrinol Metab, 2001, 86(1): 59-65.
[53]	Soyaltin UE, Simsir IY, Akinci B, Altay C, Adiyaman SC, Lee K, Onay H, Oral EA. Homozygous LMNA p.R582H pathogenic variant reveals increasing effect on the severity of fat loss in lipodystrophy. Clin Diabetes Endocrinol, 2020, 6: 13. doi: 10.1186/s40842-020-00100-9 pmid: 32685188
[54]	Vigouroux C, Magré J, Vantyghem MC, Bourut C, Lascols O, Shackleton S, Lloyd DJ, Guerci B, Padova G, Valensi P, Grimaldi A, Piquemal R, Touraine P, Trembath RC, Capeau J. Lamin A/C gene: sex-determined expression of mutations in Dunnigan-type familial partial lipodystrophy and absence of coding mutations in congenital and acquired generalized lipoatrophy. Diabetes, 2000, 49(11): 1958-1962. pmid: 11078466
[55]	Hegele RA, Cao H, Anderson CM, Hramiak IM. Heterogeneity of nuclear lamin A mutations in Dunnigan- type familial partial lipodystrophy. J Clin Endocrinol Metab, 2000. 85(9): 3431-3435.
[56]	Araújo-Vilar D, Lado-Abeal J, Palos-Paz F, Lattanzi G, Bandín MA, Bellido D, Domínguez-Gerpe L, Calvo C, Pérez O, Ramazanova A, Martínez-Sánchez N, Victoria B, Costa-Freitas AT. A novel phenotypic expression associated with a new mutation in LMNA gene, characterized by partial lipodystrophy, insulin resistance, aortic stenosis and hypertrophic cardiomyopathy. Clin Endocrinol (Oxf), 2008, 69(1): 61-68. doi: 10.1111/j.1365-2265.2007.03146.x
[57]	Resende ATP, Martins CS, Bueno AC, Moreira AC, Foss-Freitas MC, de Castro M. Phenotypic diversity and glucocorticoid sensitivity in patients with familial partial lipodystrophy type 2. Clin Endocrinol (Oxf), 2019, 91(1): 94-103.
[58]	Rankin J, Auer-Grumbach M, Bagg W, Colclough K, Nguyen TD, Fenton-May J, Hattersley A, Hudson J, Jardine P, Josifova D, Longman C, McWilliam R, Owen K, Walker M, Wehnert M, Ellard S. Extreme phenotypic diversity and nonpenetrance in families with the LMNA gene mutation R644C. Am J Med Genet A, 2008, 146A(12): 1530-1542. doi: 10.1002/ajmg.a.32331 pmid: 18478590
[59]	Monteiro LZ, Foss-Freitas MC, Júnior Montenegro RM, Foss MC. Body fat distribution in women with familial partial lipodystrophy caused by mutation in the lamin A/C gene. Indian J Endocrinol Metab, 2012, 16(1): 136-138. doi: 10.4103/2230-8210.91209 pmid: 22276265
[60]	Le Dour C, Schneebeli S, Bakiri F, Darcel F, Jacquemont ML, Maubert MA, Auclair M, Jeziorowska D, Reznik Y, Béréziat V, Capeau J, Lascols O, Vigouroux C. A homozygous mutation of prelamin-A preventing its farnesylation and maturation leads to a severe lipodystrophic phenotype: new insights into the pathogenicity of nonfarnesylated prelamin-A. J Clin Endocrinol Metab, 2011, 96(5): E856-E862. doi: 10.1210/jc.2010-2234
[61]	Hussain I, Patni N, Garg A. Lipodystrophies, dyslipidaemias and atherosclerotic cardiovascular disease. Pathology, 2019, 51(2): 202-212. doi: 10.1016/j.pathol.2018.11.004
[62]	Lazarte J, Jurgens SJ, Choi SH, Khurshid S, Morrill VN, Weng L-C, Nauffal V, Pirruccello JP, Halford JL, Hegele RA, Ellinor PT, Lunetta KL, Lubitz SA. LMNA Variants and Risk of Adult-Onset Cardiac Disease. J Am Coll Cardio, 2022, 80(1): 50-59. doi: 10.1016/j.jacc.2022.04.035
[63]	Glöcklhofer CR, Steinfurt J, Franke G, Hoppmann A, Glantschnig T, Perez-Feliz S, Alter S, Fischer J, Brunner M, Rainer PP, Köttgen A, Bode C, Odening KE. A novel LMNA nonsense mutation causes two distinct phenotypes of cardiomyopathy with high risk of sudden cardiac death in a large five-generation family. Europace, 2018, 20(12): 2003-2013. doi: 10.1093/europace/euy127 pmid: 29947763
[64]	Forissier JF, Bonne G, Bouchier C, Duboscq-Bidot L, Richard P, Wisnewski C, Briault S, Moraine C, Dubourg O, Schwartz K, Komajda M. Apical left ventricular aneurysm without atrio-ventricular block due to a lamin A/C gene mutation. Eur J Heart Fail, 2003, 5(6): 821-825. doi: 10.1016/S1388-9842(03)00149-1
[65]	Kumar S, Baldinger SH, Gandjbakhch E, Maury P, Sellal JM, Androulakis AF, Waintraub X, Charron P, Rollin A, Richard P, Stevenson WG, Macintyre CJ, Ho CY, Thompson T, Vohra JK, Kalman JM, Zeppenfeld K, Sacher F, Tedrow UB, Lakdawala NK. Long-term arrhythmic and nonarrhythmic Outcomes of Lamin A/C Mutation carriers. J Am Coll Cardiol, 2016, 68(21): 2299-2307. doi: S0735-1097(16)36236-2 pmid: 27884249
[66]	van Berlo JH, de Voogt WG, van der Kooi AJ, van Tintelen JP, Bonne G, Yaou RB, Duboc D, Rossenbacker T, Heidbüchel H, de Visser M, Crijns HJ, Pinto YM. Meta-analysis of clinical characteristics of 299 carriers of LMNA gene mutations: do lamin A/C mutations portend a high risk of sudden death? J Mol Med (Berl), 2005, 83(1): 79-83. doi: 10.1007/s00109-004-0589-1
[67]	Sidhu K, Castrini AI, Parikh V, Reza N, Owens A, Tremblay-Gravel M, Wheeler MT, Mestroni L, Taylor M, Graw S, Gigli M, Merlo M, Paldino A, Sinagra G, Judge DP, Ramos H, Mesubi O, Brown E, Turnbull S, Kumar S, Roy D, Tedrow UB, Ngo L, Haugaa K, Lakdawala NK., The response to cardiac resynchronization therapy in LMNA cardiomyopathy. Eur J Heart Fail, 2022, 24(4): 685-693. doi: 10.1002/ejhf.2463
[68]	Menezes MP, Waddell LB, Evesson FJ, Cooper S, Webster R, Jones K, Mowat D, Kiernan MC, Johnston HM, Corbett A, Harbord M, North KN, Clarke NF. Importance and challenge of making an early diagnosis in LMNA- related muscular dystrophy. Neurology, 2012, 78(16): 1258-1263. doi: 10.1212/WNL.0b013e318250d839 pmid: 22491857
[69]	Spuler S, Kalbhenn T, Zabojszcza J, van Landeghem FK, Ludtke A, Wenzel K, Koehnlein M, Schuelke M, Lüdemann L, Schmidt HH. Muscle and nerve pathology in Dunnigan familial partial lipodystrophy. Neurology, 2007, 68(9): 677-683. pmid: 17325275
[70]	McPherson E, Turner L, Zador I, Reynolds K, Macgregor D, Giampietro PF. Ovarian failure and dilated cardiomyopathy due to a novel lamin mutation. Am J Med Genet A, 2009, 149A(4): 567-572. doi: 10.1002/ajmg.a.32627 pmid: 19283854
[71]	Gambineri A, Zanotti L. Polycystic ovary syndrome in familial partial lipodystrophy type 2 (FPLD2): basic and clinical aspects. Nucleus, 2018, 9(1): 392-397. doi: 10.1080/19491034.2018.1509659 pmid: 30131000
[72]	Thong KM, Xu YX, Cook J, Takou A, Wagner B, Kawar B, Ong AC. Cosegregation of focal segmental glomerulosclerosis in a family with familial partial lipodystrophy due to a mutation in LMNA. Nephron Clin Pract, 2013, 124(1-2): 31-37. doi: 10.1159/000354716 pmid: 24080738
[73]	Owen KR, Donohoe M, Ellard S, Clarke TJ, Nicholls AJ, Hattersley AT, Bingham C. Mesangiocapillary glomerulonephritis type 2 associated with familial partial lipodystrophy (Dunnigan-Kobberling syndrome). Nephron Clin Pract, 2004, 96(2): c35-c38. doi: 10.1159/000076396 pmid: 14988595
[74]	Nicolas HA, Akimenko MA, Tesson F. Cellular and animal models of striated muscle laminopathies. Cells, 2019, 8(4): 291. doi: 10.3390/cells8040291
[75]	Young SG, Fong LG, Michaelis S. Prelamin A, Zmpste24, misshapen cell nuclei, and progeria—new evidence suggesting that protein farnesylation could be important for disease pathogenesis. J Lipid Res, 2005, 46(12): 2531-2558. doi: 10.1194/jlr.R500011-JLR200
[76]	Rusiñol AE, Sinensky MS. Farnesylated lamins, progeroid syndromes and farnesyl transferase inhibitors. J Cell Sci, 2006, 119(Pt 16): 3265-3272. pmid: 16899817
[77]	Broers JLV, Ramaekers FC, Bonne G, Yaou RB, Hutchison CJ. Nuclear lamins: laminopathies and their role in premature ageing. Physiol Rev, 2006, 86(3): 967-1008. pmid: 16816143
[78]	Cau P, Navarro C, Harhouri K, Roll P, Sigaudy S, Kaspi E, Perrin S, De Sandre-Giovannoli A, Lévy N. Nuclear matrix, nuclear envelope and premature aging syndromes in a translational research perspective. Semin Cell Dev Biol, 2014, 29: 125-147. doi: 10.1016/j.semcdb.2014.03.021 pmid: 24662892
[79]	Caron M, Auclair M, Donadille B, Béréziat V, Guerci B, Laville M, Narbonne H, Bodemer C, Lascols O, Capeau J, Vigouroux C. Human lipodystrophies linked to mutations in A-type lamins and to HIV protease inhibitor therapy are both associated with prelamin A accumulation, oxidative stress and premature cellular senescence. Cell Death Differ, 2007, 14(10): 1759-1767. pmid: 17612587
[80]	Bidault G, Garcia M, Vantyghem MC, Ducluzeau PH, Morichon R, Thiyagarajah K, Moritz S, Capeau J, Vigouroux C, Béréziat V. Lipodystrophy-linked LMNA p.R482W mutation induces clinical early atherosclerosis and in vitro endothelial dysfunction. Arterioscler Thromb Vasc Biol, 2013, 33(9): 2162-2171. doi: 10.1161/ATVBAHA.113.301933
[81]	Lloyd DJ, Trembath RC, Shackleton S. A novel interaction between lamin A and SREBP1: implications for partial lipodystrophy and other laminopathies. Hum Mol Genet, 2002, 11(7): 769-777. pmid: 11929849
[82]	Meyer SU, Sass S, Mueller NS, Krebs S, Bauersachs S, Kaiser S, Blum H, Thirion C, Krause S, Theis FJ, Pfaffl MW. Integrative analysis of microRNA and mRNA data reveals an orchestrated function of microRNAs in skeletal myocyte differentiation in response to TNF-α or IGF1. PLoS One, 2015, 10(8): e0135284. doi: 10.1371/journal.pone.0135284
[83]	Tomé M, López-Romero P, Albo C, Sepúlveda JC, Fernández-Gutiérrez B, Dopazo A, Bernad A, González MA. miR-335 orchestrates cell proliferation, migration and differentiation in human mesenchymal stem cells. Cell Death Differ, 2011, 18(6): 985-995. doi: 10.1038/cdd.2010.167 pmid: 21164520
[84]	Oldenburg A, Briand N, Sørensen AL, Cahyani I, Shah A, Moskaug J, Collas P. A lipodystrophy-causing lamin A mutant alters conformation and epigenetic regulation of the anti-adipogenic MIR335 locus. J Cell Biol, 2017, 216(9): 2731-2743. doi: 10.1083/jcb.201701043 pmid: 28751304
[85]	Choi JC, Muchir A, Wu W, Iwata S, Homma S, Morrow JP, Worman HJ. Temsirolimus activates autophagy and ameliorates cardiomyopathy caused by lamin A/C gene mutation. Sci Transl Med, 2012, 4(144): 144ra102.
[86]	Ramos FJ, Chen SC, Garelick MG, Dai DF, Liao CY, Schreiber KH, MacKay VL, An EH, Strong R, Ladiges WC, Rabinovitch PS, Kaeberlein M, Kennedy BK. Rapamycin reverses elevated mTORC1 signaling in lamin A/C-deficient mice, rescues cardiac and skeletal muscle function, and extends survival. Sci Transl Med, 2012, 4(144): 144ra103.
[87]	Chartoumpekis DV, Palliyaguru DL, Wakabayashi N, Khoo NK, Schoiswohl G, O'Doherty RM, Kensler TW. Notch intracellular domain overexpression in adipocytes confers lipodystrophy in mice. Mol Metab, 2015, 4(7): 543-550. doi: 10.1016/j.molmet.2015.04.004 pmid: 26137442
[88]	Perepelina K, Dmitrieva R, Ignatieva E, Borodkina A, Kostareva A, Malashicheva A. Lamin A/C mutation associated with lipodystrophy influences adipogenic differentiation of stem cells through interaction with Notch signaling. Biochem Cell Biol, 2018, 96(3): 342-348. doi: 10.1139/bcb-2017-0210 pmid: 29040816
[89]	Le Dour C, Wu W, Béréziat V, Capeau J, Vigouroux C, Worman HJ. Extracellular matrix remodeling and transforming growth factor-β signaling abnormalities induced by lamin A/C variants that cause lipodystrophy. J Lipid Res, 2017, 58(1): 151-163. doi: 10.1194/jlr.M071381 pmid: 27845687
[90]	Muchir A, Medioni J, Laluc M, Massart C, Arimura T, van der Kooi AJ, Desguerre I, Mayer M, Ferrer X, Briault S, Hirano M, Worman HJ, Mallet A, Wehnert M, Schwartz K, Bonne G. Nuclear envelope alterations in fibroblasts from patients with muscular dystrophy, cardiomyopathy, and partial lipodystrophy carrying lamin A/C gene mutations. Muscle Nerve, 2004, 30(4): 444-450. pmid: 15372542
[91]	Vigouroux C, Guénantin AC, Vatier C, Capel E, Le Dour C, Afonso P, Bidault G, Béréziat V, Lascols O, Capeau J, Briand N, Jéru I. Lipodystrophic syndromes due to LMNA mutations: recent developments on biomolecular aspects, pathophysiological hypotheses and therapeutic perspectives. Nucleus, 2018, 9(1): 235-248. doi: 10.1080/19491034.2018.1456217 pmid: 29578370
[92]	Foss-Freitas MC, Akinci B, Luo YY, Stratton A, Oral EA. Diagnostic strategies and clinical management of lipodystrophy. Expert Rev Endocrinol Metab, 2020, 15(2): 95-114. doi: 10.1080/17446651.2020.1735360 pmid: 32368944
[93]	Vatier C, Fetita S, Boudou P, Tchankou C, Deville L, Riveline J, Young J, Mathivon L, Travert F, Morin D, Cahen J, Lascols O, Andreelli F, Reznik Y, Mongeois E, Madelaine I, Vantyghem M, Gautier J, Vigouroux C. One-year metreleptin improves insulin secretion in patients with diabetes linked to genetic lipodystrophic syndromes. Diabetes Obes Metab, 2016, 18(7): 693-697. doi: 10.1111/dom.12606 pmid: 26584826
[94]	Grundfest-Broniatowski S, Yan JL, Kroh M, Kilim H, Stephenson A. Successful treatment of an unusual case of FPLD2:the role of Roux-en-Y gastric bypass-case report and literature review. J Gastrointest Surg, 2017, 21(4): 739-743.
[95]	Boettcher E, Csako G, Pucino F, Wesley R, Loomba R. Meta-analysis: pioglitazone improves liver histology and fibrosis in patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther, 2012, 35(1): 66-75. doi: 10.1111/j.1365-2036.2011.04912.x
[96]	Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, Neuschwander-Tetri BA, Lavine JE, Tonascia J, Unalp A, Van Natta M, Clark J, Brunt EM, Kleiner DE, Hoofnagle JH, Robuck PR, NASH CRN. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med, 2010, 362(18): 1675-1685. doi: 10.1056/NEJMoa0907929

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LMNA基因突变相关脂肪萎缩综合征的研究进展

Advances in lipodystrophy syndrome caused by LMNA gene mutation

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