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

Hung Fat Tse; Jenny C.Y. Ho; Shing Wan Choi; Yee Ki Lee; Amy W. Butler; Kwong Man Ng; Chung Wah Siu; Michael A. Simpson; Wing Hon Lai; Yau Chi Chan; Ka Wing Au; Jinqiu Zhang; Kenneth W.J. Lay; Miguel A. Esteban; John M. Nicholls; Alan Colman; Pak C. Sham

doi:10.1093/hmg/dds556

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

Hung Fat Tse, Jenny C.Y. Ho, Shing Wan Choi, Yee Ki Lee, Amy W. Butler, Kwong Man Ng, Chung Wah Siu, Michael A. Simpson, Wing Hon Lai, Yau Chi Chan, Ka Wing Au, Jinqiu Zhang, Kenneth W.J. Lay, Miguel A. Esteban, John M. Nicholls, Alan Colman, Pak C. Sham

Research output: Contribution to journal › Article › peer-review

91 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	1395-1403
Number of pages	9
Journal	Human Molecular Genetics
Volume	22
Issue number	7
DOIs	https://doi.org/10.1093/hmg/dds556
State	Published - Apr 2013
Externally published	Yes

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Tse, H. F., Ho, J. C. Y., Choi, S. W., Lee, Y. K., Butler, A. W., Ng, K. M., Siu, C. W., Simpson, M. A., Lai, W. H., Chan, Y. C., Au, K. W., Zhang, J., Lay, K. W. J., Esteban, M. A., Nicholls, J. M., Colman, A., & Sham, P. C. (2013). 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. Human Molecular Genetics, 22(7), 1395-1403. https://doi.org/10.1093/hmg/dds556

@article{a3ea8a4f3a704c649bfddb98d1174d58,

title = "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",

abstract = "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.",

author = "Tse, \{Hung Fat\} and Ho, \{Jenny C.Y.\} and Choi, \{Shing Wan\} and Lee, \{Yee Ki\} and Butler, \{Amy W.\} and Ng, \{Kwong Man\} and Siu, \{Chung Wah\} and Simpson, \{Michael A.\} and Lai, \{Wing Hon\} and Chan, \{Yau Chi\} and Au, \{Ka Wing\} and Jinqiu Zhang and Lay, \{Kenneth W.J.\} and Esteban, \{Miguel A.\} and Nicholls, \{John M.\} and Alan Colman and Sham, \{Pak C.\}",

year = "2013",

month = apr,

doi = "10.1093/hmg/dds556",

language = "English",

volume = "22",

pages = "1395--1403",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "7",

}

Tse, HF, Ho, JCY, Choi, SW, Lee, YK, Butler, AW, Ng, KM, Siu, CW, Simpson, MA, Lai, WH, Chan, YC, Au, KW, Zhang, J, Lay, KWJ, Esteban, MA, Nicholls, JM, Colman, A & Sham, PC 2013, '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', Human Molecular Genetics, vol. 22, no. 7, pp. 1395-1403. https://doi.org/10.1093/hmg/dds556

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. / Tse, Hung Fat; Ho, Jenny C.Y.; Choi, Shing Wan et al.
In: Human Molecular Genetics, Vol. 22, No. 7, 04.2013, p. 1395-1403.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - 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

AU - Tse, Hung Fat

AU - Ho, Jenny C.Y.

AU - Choi, Shing Wan

AU - Lee, Yee Ki

AU - Butler, Amy W.

AU - Ng, Kwong Man

AU - Siu, Chung Wah

AU - Simpson, Michael A.

AU - Lai, Wing Hon

AU - Chan, Yau Chi

AU - Au, Ka Wing

AU - Zhang, Jinqiu

AU - Lay, Kenneth W.J.

AU - Esteban, Miguel A.

AU - Nicholls, John M.

AU - Colman, Alan

AU - Sham, Pak C.

PY - 2013/4

Y1 - 2013/4

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/84875276852

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SN - 0964-6906

VL - 22

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EP - 1403

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 7

ER -

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

Abstract

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