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.