Novel LMNA Mutations in Greek and Myanmar Patients with Progeroid Features and Cardiac Manifestations

Overview

Journal Aging Pathobiol Ther

Date 2020 Sep 21

PMID 32954377

Citations 3

Authors

Renuka Kandhaya-Pillai

Fuki M Hisama

Stephanie A Bucks

Soe Yarzar

Haroula Korovou

George M Martin

Junko Oshima

Affiliations

Soon will be listed here.

Abstract

Segmental progeroid syndromes are groups of genetic disorders with multiple features resembling accelerated aging. The International Registry of Werner Syndrome (Seattle, WA) recruits pedigrees of progeroid syndromes from all over the world. We identified two novel LMNA mutations, p.Asp300Gly in a patient from Myanmar, and p.Asn466Lys, in a patient from Greece. Both were referred to our Registry for the genetic diagnosis because of the accelerated aged-appearance and cardiac complications. LMNA mutations are the second most common genetic cause of progeroid syndromes after WRN mutations in our Registry. As the next generation sequencing becomes readily available, we expect to identify more cases of rare genetic diseases in the developing countries.

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References

Cattin M, Muchir A, Bonne G . 'State-of-the-heart' of cardiac laminopathies. Curr Opin Cardiol. 2013; 28(3):297-304. DOI: 10.1097/HCO.0b013e32835f0c79. View

Buchwalter A, Kaneshiro J, Hetzer M . Coaching from the sidelines: the nuclear periphery in genome regulation. Nat Rev Genet. 2018; 20(1):39-50. PMC: 6355253. DOI: 10.1038/s41576-018-0063-5. View

Mory P, Crispim F, Freire M, Salles J, Valerio C, Godoy-Matos A . Phenotypic diversity in patients with lipodystrophy associated with LMNA mutations. Eur J Endocrinol. 2012; 167(3):423-31. DOI: 10.1530/EJE-12-0268. View

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J . Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015; 17(5):405-24. PMC: 4544753. DOI: 10.1038/gim.2015.30. View

Worman H, Bonne G . "Laminopathies": a wide spectrum of human diseases. Exp Cell Res. 2007; 313(10):2121-33. PMC: 2964355. DOI: 10.1016/j.yexcr.2007.03.028. View

Akinrinade O, Ollila L, Vattulainen S, Tallila J, Gentile M, Salmenpera P . Genetics and genotype-phenotype correlations in Finnish patients with dilated cardiomyopathy. Eur Heart J. 2015; 36(34):2327-37. PMC: 4561350. DOI: 10.1093/eurheartj/ehv253. View

Kircher M, Witten D, Jain P, ORoak B, Cooper G, Shendure J . A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet. 2014; 46(3):310-5. PMC: 3992975. DOI: 10.1038/ng.2892. View

Captur G, Arbustini E, Bonne G, Syrris P, Mills K, Wahbi K . Lamin and the heart. Heart. 2017; 104(6):468-479. DOI: 10.1136/heartjnl-2017-312338. View

Yokote K, Chanprasert S, Lee L, Eirich K, Takemoto M, Watanabe A . WRN Mutation Update: Mutation Spectrum, Patient Registries, and Translational Prospects. Hum Mutat. 2016; 38(1):7-15. PMC: 5237432. DOI: 10.1002/humu.23128. View

10.

Adzhubei I, Jordan D, Sunyaev S . Predicting functional effect of human missense mutations using PolyPhen-2. Curr Protoc Hum Genet. 2013; Chapter 7:Unit7.20. PMC: 4480630. DOI: 10.1002/0471142905.hg0720s76. View

11.

Tobita T, Nomura S, Fujita T, Morita H, Asano Y, Onoue K . Genetic basis of cardiomyopathy and the genotypes involved in prognosis and left ventricular reverse remodeling. Sci Rep. 2018; 8(1):1998. PMC: 5792481. DOI: 10.1038/s41598-018-20114-9. View

12.

Dobrzynska A, Gonzalo S, Shanahan C, Askjaer P . The nuclear lamina in health and disease. Nucleus. 2016; 7(3):233-48. PMC: 4991244. DOI: 10.1080/19491034.2016.1183848. View

13.

Chen L, Lee L, Kudlow B, Dos Santos H, Sletvold O, Shafeghati Y . LMNA mutations in atypical Werner's syndrome. Lancet. 2003; 362(9382):440-5. DOI: 10.1016/S0140-6736(03)14069-X. View

14.

Doubaj Y, De Sandre-Giovannoli A, Vera E, Navarro C, Elalaoui S, Tajir M . An inherited LMNA gene mutation in atypical Progeria syndrome. Am J Med Genet A. 2012; 158A(11):2881-7. DOI: 10.1002/ajmg.a.35557. View

15.

Hisama F, Lessel D, Leistritz D, Friedrich K, McBride K, Pastore M . Coronary artery disease in a Werner syndrome-like form of progeria characterized by low levels of progerin, a splice variant of lamin A. Am J Med Genet A. 2011; 155A(12):3002-6. PMC: 4679285. DOI: 10.1002/ajmg.a.34336. View

16.

Renard D, Fourcade G, Milhaud D, Bessis D, Esteves-Vieira V, Boyer A . Novel LMNA mutation in atypical Werner syndrome presenting with ischemic disease. Stroke. 2008; 40(2):e11-4. DOI: 10.1161/STROKEAHA.108.531780. View

17.

van Steensel B, Belmont A . Lamina-Associated Domains: Links with Chromosome Architecture, Heterochromatin, and Gene Repression. Cell. 2017; 169(5):780-791. PMC: 5532494. DOI: 10.1016/j.cell.2017.04.022. View

18.

Saha B, Lessel D, Hisama F, Leistritz D, Friedrich K, Martin G . 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. PMC: 2957848. DOI: 10.1159/000320166. View

19.

Haas J, Frese K, Peil B, Kloos W, Keller A, Nietsch R . Atlas of the clinical genetics of human dilated cardiomyopathy. Eur Heart J. 2014; 36(18):1123-35a. DOI: 10.1093/eurheartj/ehu301. View

20.

Nguyen D, Leistritz D, Turner L, MacGregor D, Ohson K, Dancey P . Collagen expression in fibroblasts with a novel LMNA mutation. Biochem Biophys Res Commun. 2006; 352(3):603-8. PMC: 1867458. DOI: 10.1016/j.bbrc.2006.11.070. View