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Pediatrics - Cardiology

Houston, Texas

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Pediatrics - Cardiology
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TAZ (G4.5) Mutation Analysis

Left Ventricle of a LVNC heartBarth 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 that 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 are 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.

Reasons for Referral

  • Molecular confirmation of the diagnosis of Barth syndrome, X-linked infantile cardiomyopathy, left ventricular noncompaction and X-linked endocardial fibroelastosis in affected males.
  • Carrier testing in females with a family history of Barth syndrome, X-linked infantile cardiomyopathy, left ventricular noncompaction and X-linked endocardial fibroelastosis.
  • Carrier testing is not offered for asymptomatic minor females. Please call for additional information.

Methodology

Genomic DNA is analyzed for TAZ mutations by automatic fluorescent DNA sequencing of all 11 exons of the TAZ gene, as well as the exon/intron junctions and a portion of the 5′ and 3′ untranslated regions. Patient DNA is sequenced in both the forward and reverse orientations. If a mutation is identified, additional family members are analyzed only for the familial mutation by automatic fluorescent DNA sequencing.

Service Fees

Service Direct and Institutional Billing CPT Codes
Index Case (Male or Female) $600 per sample 81406, G0452
Additional Family Members $300 per sample; known familial mutation only 81403, G0452

Sensitivity

DNA Sequencing Analysis: Approximately 99 percent detection of mutations in exons 1-11 of TAZ.

Specimen Requirements

Blood (preferred): EDTA (purple-top) tubes: Adult: 5 cc, Child: 5 cc, Infant: 2-3 cc
Tissue: Frozen (preferred), RNAlater, Formalin-fixed, Paraffin-embedded
Other Body Fluids: Call to inquire
Buccal Swabs: One swab from each cheek

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