Novel Adult-Onset Systolic Cardiomyopathy Due to MYH7 E848G Mutation in Patient-Derived Induced Pluripotent Stem Cells
Kai-Chun Yang, Astrid Breitbart, Willem J. De Lange, Peter Hofsteen, Akiko Futakuchi-Tsuchida, Joy Xu, Cody Schopf, Maria V. Razumova, Alex Jiao, Robert Boucek, Lil Pabon, Hans Reinecke, Deok-Ho Kim, J. Carter Ralphe, Michael Regnier and Charles E. Murry
Derivation and Characterization of Patient-Specific FCM iPSC-CMs
(A) Pedigree of the familial cardiomyopathy (FCM) with the myosin heavy chain 7 (MYH7) E848G missense mutation in this study. Solid symbols indicate echocardiographic evidence of systolic impairment; “+” and “-” represent the presence and absence of the MYH7 E848G mutation, respectively. The red border indicates the inclusion of the individual’s induced pluripotent stem cells (iPSCs) in this study. (B) Deoxyribonucleic acid sequencing confirms MYH7 E848G heterozygous mutation in the FCM patients and the absence of the mutation in the control (Con) subjects. (C) Representative images of fibroblasts from a skin biopsy sample (left), the iPSC colony obtained after episomally reprogramming dermal fibroblasts (middle), and alkaline phosphatase (Alk Phos) staining of the patient-specific iPSC colony (right). (D) Representative flow cytometry of 2 pluripotency markers, SSEA4 and GCTM2, in an iPSC line with (E) quantification of double-positive population in all 6 patient-specific iPSC lines. CM = cardiomyocytes; Phase = phase microscopy; WT = wild type.