A Novel Exonic Splicing Mutation in the TAZ (G4.5) Gene in a Case with Atypical Barth Syndrome

Research Report
Part of the JIMD Reports book series (JIMD, volume 11)


Objective: Barth syndrome is an X-linked recessive disorder characterized by dilated cardiomyopathy, neutropenia, 3-methylglutaconic aciduria, abnormal mitochondria, variably expressed skeletal myopathy, and growth delay. The disorder is caused by mutations in the tafazzin (TAZ/G4.5) gene located on Xq28. We report a novel exonic splicing mutation in the TAZ gene in a patient with atypical Barth syndrome.

Patient & Methods: The 4-month-old proband presented with respiratory distress, neutropenia, and dilated cardiomyopathy with reduced ejection fraction of 10%. No 3-methylglutaconic aciduria was detected on repeated urine organic acid analyses. Family history indicated that his maternal uncle died of endocardial fibroelastosis and dilated cardiomyopathy at 26 months. TAZ DNA sequencing, mRNA analysis, and cardiolipin analysis were performed.

Results: A novel nucleotide substitution c.553A>G in exon 7 of the TAZ gene was identified in the proband, predicting an amino acid substitution p.Met185Val. However, this mutation created a new splice donor signal within exon 7 causing mis-splicing of the message, producing two messages that only differ in the presence/absence of exon 5; these retain intron 6 and have only 11 bases of exon 7. Cardiolipin analysis confirmed the loss of tafazzin activity. The proband’s mother, maternal aunt, and grandmother carry the same mutation.

Conclusions: The identification of a TAZ gene mutation, mRNA analysis, and monolysocardiolipin/cardiolipin ratio determination were important for the diagnosis and genetic counseling in this family with atypical Barth syndrome that was not found to be associated with 3-methylglutaconic aciduria.


Dilate Cardiomyopathy Brain Natriuretic Peptide Barth Syndrome Indirect Flight Muscle Maternal Aunt 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



3-methylglutaconic acid


Brain natriuretic peptide


Barth Syndrome


High sensitivity C-reactive protein






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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.John Welsh Cardiovascular Diagnostic Laboratory, Section of Cardiology, Department of PediatricsTexas Children’s Hospital, Baylor College of MedicineHoustonUSA
  2. 2.Division of Metabolic DisordersChildren’s Hospital of Orange CountyOrange CountyUSA
  3. 3.Children’s Hospital of Orange County and Department of PediatricsUniversity of California IrvineOrangeUSA
  4. 4.Department of PediatricsUniversity of CaliforniaLos AngelesUSA
  5. 5.Nemours Biomedical Research DepartmentAlfred I. duPont Hospital for ChildrenWilmingtonUSA
  6. 6.Department of PathologyUniversity of CaliforniaLos AngelesUSA
  7. 7.Department of Clinical ChemistryUniversity of Amsterdam, Laboratory Genetic Metabolic DiseasesAmsterdamThe Netherlands
  8. 8.Linda Crnic Institute for Down SyndromeUniversity of Colorado School of MedicineAuroraUSA
  9. 9.UCI Division of Genetics and Metabolism, Dept. of PediatricsUniv. of California-Irvine Med. CenterOrangeUSA

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