Patient-specific induced-pluripotent stem cells-derived cardiomyocytes recapitulate the pathogenic phenotypes of dilated cardiomyopathy due to a novel DES mutation identified by whole exome sequencing

被引：80

作者：

Tse, Hung-Fat ^{[1
,2
,11
,12
]}

Ho, Jenny C. Y. ^{[1
,2
]}

Choi, Shing-Wan ^{[3
]}

Lee, Yee-Ki ^{[1
]}

Butler, Amy W. ^{[3
,7
]}

Ng, Kwong-Man ^{[1
]}

Siu, Chung-Wah ^{[1
,2
]}

Simpson, Michael A. ^{[8
]}

Lai, Wing-Hon ^{[1
]}

Chan, Yau-Chi ^{[1
]}

Au, Ka-Wing ^{[1
]}

Zhang, Jinqiu ^{[9
]}

Lay, Kenneth W. J. ^{[9
]}

Esteban, Miguel A. ^{[10
,11
,12
]}

Nicholls, John M. ^{[4
]}

Colman, Alan ^{[9
]}

Sham, Pak C. ^{[3
,5
,6
]}

机构：

[1] Univ Hong Kong, Queen Mary Hosp, Dept Med, Div Cardiol, Hong Kong, Hong Kong, Peoples R China

[2] Univ Hong Kong, Res Ctr Heart Brain Hormone & Hlth Aging, Hong Kong, Hong Kong, Peoples R China

[3] Univ Hong Kong, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China

[4] Univ Hong Kong, Dept Pathol, Hong Kong, Hong Kong, Peoples R China

[5] Univ Hong Kong, Ctr Genom Sci, Hong Kong, Hong Kong, Peoples R China

[6] Univ Hong Kong, Li Ka Shing Fac Med, State Key Lab Cognit & Brain Sci, Hong Kong, Hong Kong, Peoples R China

[7] Kings Coll London, Inst Psychiat, MRC Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England

[8] Kings Coll London, Sch Med, Guys Hosp, Div Genet & Mol Med, London WC2R 2LS, England

[9] ASTAR, Inst Med Biol, Stem Cell Dis Models, Singapore, Singapore

[10] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, South China Inst Stem Cell Biol & Regenerat Med, Key Lab Regenerat Biol, Guangzhou, Guangdong, Peoples R China

[11] Univ Hong Kong, Hong Kong Guangdong Joint Lab Stem Cell & Regener, Hong Kong, Hong Kong, Peoples R China

[12] Guangzhou Inst Biomed & Hlth, Guangzhou, Peoples R China

来源：

HUMAN MOLECULAR GENETICS | 2013年 / 22卷 / 07期

关键词：

SKELETAL; GENERATION; MYOPATHY;

D O I：

10.1093/hmg/dds556

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In this paper, we report a novel heterozygous mutation of A285V codon conversion on exon 4 of the desmin (DES), using whole exome sequencing (WES) in an isolated proband with documented dilated cardiomyopathy (DCM). This mutation is predicted to cause three-dimensional structure changes of DES. Immunohistological and electron microscopy studies demonstrated diffuse abnormal DES aggregations in DCM-induced-pluripotent stem cell (iPSC)-derived cardiomyocytes, and control-iPSC-derived cardiomyocytes transduced with A285V-DES. DCM-iPSC-derived cardiomyocytes also exhibited functional abnormalities in vitro. This is the first demonstration that patient-specific iPSC-derived cardiomyocytes can be used to provide histological and functional confirmation of a suspected genetic basis for DCM identified by WES.

引用

页码：1395 / 1403

页数：9

共 27 条

[1] Exome sequencing as a tool for Mendelian disease gene discovery [J].

Bamshad, Michael J. ;

Ng, Sarah B. ;

Bigham, Abigail W. ;

Tabor, Holly K. ;

Emond, Mary J. ;

Nickerson, Deborah A. ;

Shendure, Jay .

NATURE REVIEWS GENETICS, 2011, 12 (11) :745-755

[2] Desmin myopathy, a skeletal myopathy with cardiomyopathy caused by mutations in the desmin gene. [J].

Dalakas, MC ;

Park, KY ;

Semino-Mora, C ;

Lee, HS ;

Sivakumar, K ;

Goldfarb, LG .

NEW ENGLAND JOURNAL OF MEDICINE, 2000, 342 (11) :770-780

[3] Tragedy in a heartbeat: malfunctioning desmin causes skeletal and cardiac muscle disease [J].

Goldfarb, Lev G. ;

Dalakas, Marinos C. .

JOURNAL OF CLINICAL INVESTIGATION, 2009, 119 (07) :1806-1813

[4] Variable pathogenic potentials of mutations located in the desmin alpha-helical domain [J].

Goudeau, Bertrand ;

Rodrigues-Lima, Fernando ;

Fischer, Dirk ;

Casteras-Simon, Monique ;

Sambuughin, Nyamkhishig ;

de Visser, Marianne ;

Laforet, Pascal ;

Ferrer, Xavier ;

Chapon, Francoise ;

Sjoberg, Gunnar ;

Kostareva, Anna ;

Sejersen, Thomas ;

Dalakas, Marinos C. ;

Goldfarb, Lev G. ;

Vicart, Patrick .

HUMAN MUTATION, 2006, 27 (09) :906-913

[5] Autosomal dominant myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy 7 is caused by a DES mutation [J].

Hedberg, Carola ;

Melberg, Atle ;

Kuhl, Angelika ;

Jenne, Dieter ;

Oldfors, Anders .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2012, 20 (09) :984-985

[6] Update 2011: Clinical and Genetic Issues in Familial Dilated Cardiomyopathy [J].

Hershberger, Ray E. ;

Siegfried, Jill D. .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2011, 57 (16) :1641-1649

[7] A series of Chinese patients with desminopathy associated with six novel and one reported mutations in the desmin gene [J].

Hong, D. ;

Wang, Z. ;

Zhang, W. ;

Xi, J. ;

Lu, J. ;

Luan, X. ;

Yuan, Y. .

NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY, 2011, 37 (03) :257-270

[8] ROCK Inhibition Facilitates the Generation of Human-Induced Pluripotent Stem Cells in a Defined, Feeder-, and Serum-Free System [J].

Lai, Wing-Hon ;

Ho, Jenny Chung-Yee ;

Lee, Yee-Ki ;

Ng, Kwong-Man ;

Au, Ka-Wing ;

Chan, Yau-Chi ;

Lau, Chu-Pak ;

Tse, Hung-Fat ;

Siu, Chung-Wah .

CELLULAR REPROGRAMMING, 2010, 12 (06) :641-653

[9] Clustal W and clustal X version 2.0 [J].

Larkin, M. A. ;

Blackshields, G. ;

Brown, N. P. ;

Chenna, R. ;

McGettigan, P. A. ;

McWilliam, H. ;

Valentin, F. ;

Wallace, I. M. ;

Wilm, A. ;

Lopez, R. ;

Thompson, J. D. ;

Gibson, T. J. ;

Higgins, D. G. .

BIOINFORMATICS, 2007, 23 (21) :2947-2948

[10] Molecular autopsy in young sudden cardiac death victims with suspected cardiomyopathy [J].

Larsen, M. K. ;

Nissen, P. H. ;

Berge, K. E. ;

Leren, T. P. ;

Kristensen, I. B. ;

Jensen, H. K. ;

Banner, J. .

FORENSIC SCIENCE INTERNATIONAL, 2012, 219 (1-3) :33-38

← 1 2 3 →