TAZ (G4.5) Mutation Analysis

Barth syndrome, originally described in 1979 by Neustein et al. and later by Barth et al. as an X-linked cardioskeletal myopathy with abnormal mitochondria and neutropenia, is a severe disorder which classically presents in infancy with heart failure, sepsis, and may be associated with 3-methylglutaconic aciduria. Growth retardation, abnormalities of carnitine and cholesterol, and mitochondrial respiratory chain deficiency, particularly cytochrome C, are also notable. A high percentage of affected children reportedly succumb early in life from this disorder.

Bione et al. identified the disease-causing gene as TAZ (G4.5), a novel gene containing 11 alternatively spliced exons. The gene, which is located on the X chromosome at Xq28, encodes a protein family called tafazzins, whose function remains unknown. Multiple mutations in TAZ have been identified including missense, nonsense, and splicing mutations, as well as small deletions and insertions. However, phenotype-genotype correlations have not been identified. Further, it has been shown that mutations in TAZ not only result in classic Barth syndrome but also in left ventricular noncompaction, X-linked infantile cardiomyopathy, X-linked endocardial fibroelastosis, and dilated cardiomyopathy. Thus, mutations in TAZ can result in a broad spectrum of clinical diseases, including but not limited to classical Barth syndrome.

The John Welsh Cardiovascular Diagnostic Laboratory offers molecular genetic testing for TAZ mutations. Symptomatic males will be tested by automatic fluorescent DNA sequencing of all 11 exons of the TAZ gene. We strongly recommend initial testing of an affected male, if available, in order to provide the greatest test sensitivity and clearest interpretation of results for subsequent carrier female testing. If an affected male is unavailable for testing, testing of females at high risk is offered. Genetic counseling is recommended for all individuals in order to identify additional at-risk family members and to discuss reproductive issues.