Recessive TAF1A mutations reveal ribosomopathy in siblings with end-stage pediatric dilated cardiomyopathy

Pamela A. Long, Jeanne L. Theis, Yu Huan Shih, Joseph J. Maleszewski, Patrice C. Abell Aleff, Jared M. Evans, Xiaolei Xu, Timothy M. Olson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Non-ischemic dilated cardiomyopathy (DCM) has been recognized as a heritable disorder for over 25 years, yet clinical genetic testing is non-diagnostic in >50% of patients, underscoring the ongoing need for DCM gene discovery. Here, whole exome sequencing uncovered a novel molecular basis for idiopathic end-stage heart failure in two sisters who underwent cardiac transplantation at three years of age. Compound heterozygous recessive mutations in TAF1A, encoding an RNA polymerase I complex protein, were associated with marked fibrosis of explanted hearts and gene-specific nucleolar segregation defects in cardiomyocytes, indicative of impaired ribosomal RNA synthesis. Knockout of the homologous gene in zebrafish recapitulated a heart failure phenotype with pericardial edema, decreased ventricular systolic function, and embryonic mortality. These findings expand the clinical spectrum of ribosomopathies to include pediatric DCM.

Original languageEnglish (US)
Pages (from-to)2874-2881
Number of pages8
JournalHuman molecular genetics
Issue number15
StatePublished - Aug 1 2017

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)


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