Tafazzin gene mutations are uncommon causes of dilated cardiomyopathy in adults

  • Matthew Taylor | matthew.taylor@ucdenver.edu University of Colorado Denver, Aurora CO, United States.
  • Dobromir Slavov University of Colorado Denver, Aurora CO, United States.
  • Ernesto Salcedo University of Colorado Denver, Aurora CO, United States.
  • Xiao Zhu University of Colorado Denver, Aurora CO, United States.
  • Deborah Ferguson University of Colorado Denver, Aurora CO, United States.
  • Jean Jirikowic University of Colorado Denver, Aurora CO, United States.
  • Andrea Di Lenarda Ospedale Cattinara and University of Trieste, Trieste, Italy.
  • Gianfranco Sinagra Ospedale Cattinara and University of Trieste, Trieste, Italy.
  • Luisa Mestroni University of Colorado Denver, Aurora CO, United States.

Abstract

Barth syndrome is an X-linked genetic condition featuring neutropenia, skeletal myopathy, and dilated cardiomyopathy in boys due to tafazzin (TAZ) mutations. Pure dilated cardiomyopathy without other features of Barth syndrome may also result from TAZ mutations and survival into adulthood has been described. Although TAZ testing is routinely included in dilated cardiomyopathy panels in adults, the prevalence of TAZ mutations in the adult population, including women who may be at risk to develop later onset disease due to TAZ mutations, has not been measured. We screened 292 families with dilated cardiomyopathy (209 male and 83 female probands) for TAZ mutations using denaturing high-performance liquid chromatography and sequence analysis. Putative mutations were evaluated based on standard criteria including screening available relatives and healthy controls and for effects on splicing efficiency in the case of one intronic variant. Two variants suspicious for being pathogenic were found in two unrelated families (c.387T>C, Phe128Ser and c.507C>T, Leu169Leu). The Phe128Ser variant had been previously reported as a pathogenic mutation; however we determined that this variant is instead a rare polymorphism restricted to African Americans. The Leu169Leu variant was detected in a male patient and altered RNA processing in our minigene assay supporting a pathogenic role. No mutations in female subjects were detected. Tafazzin mutations were rare in our population of adults with dilated cardiomyopathy and none were found in females. Our findings indicate that genetic testing for tafazzin should not be routinely performed in dilated cardiomyopathy as suggested by current guidelines. Furthermore, the Phe128Ser variant is not pathogenic, but likely represents a benign polymorphism in persons of African American ancestry.

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Author Biographies

Matthew Taylor, University of Colorado Denver, Aurora CO

University of Colorado Denver, Adult Medical Genetics Program

Dobromir Slavov, University of Colorado Denver, Aurora CO

University of Colorado Denver, Adult Medical Genetics Program

Ernesto Salcedo, University of Colorado Denver, Aurora CO

University of Colorado Denver, Adult Medical Genetics Program

Xiao Zhu, University of Colorado Denver, Aurora CO

University of Colorado Denver, Adult Medical Genetics Program

Deborah Ferguson, University of Colorado Denver, Aurora CO

University of Colorado Denver, Adult Medical Genetics Program

Jean Jirikowic, University of Colorado Denver, Aurora CO

University of Colorado Denver, Adult Medical Genetics Program

Luisa Mestroni, University of Colorado Denver, Aurora CO

University of Colorado Denver, Adult Medical Genetics Program

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Published
2011-07-05
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Section
Original Articles
Supporting Agencies
Barth Syndrome Foundation
Keywords:
dilated cardiomyopathy, tafazzin, genetics, Barth syndrome, neutropenia, genetic counseling.
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How to Cite
Taylor, M., Slavov, D., Salcedo, E., Zhu, X., Ferguson, D., Jirikowic, J., Di Lenarda, A., Sinagra, G., & Mestroni, L. (2011). Tafazzin gene mutations are uncommon causes of dilated cardiomyopathy in adults. Cardiogenetics, 1(1), e4. https://doi.org/10.4081/cardiogenetics.2011.e4