The Invitae Barth Syndrome Test analyzes the TAZ gene. Pathogenic variants in this gene cause Barth syndrome, an inborn error of lipid metabolism. Genetic testing of this gene may confirm a diagnosis and help guide treatment and management decisions. Identification of a disease-causing variant would also guide testing and diagnosis of at-risk relatives.
The Invitae Organic Acidemias Panel and the Invitae Elevated C5-OH Panel have been designed to provide a broad genetic analysis of this class of disorders. Depending on the individual’s clinical and family history, one of these broader panels may be appropriate. They can be ordered at no additional cost.
Barth syndrome, also known as 3-methylglutaconic aciduria type II, is characterized by cardiomyopathy, neutropenia, skeletal myopathy, growth and/or developmental delay, and distinct facial features in affected males. Cardiomyopathy in males can present as dilated cardiomyopathy (DCM) or left ventricular noncompaction (LVNC), or in some cases as hypertrophic cardiomyopathy (HCM). Carrier females may present with cardiomyopathy—typically DCM without the other features of Barth syndrome—or may remain asymptomatic.
The TAZ gene encodes Tafazzin, an enzyme required for cardiolipin remodelling that maintains the function of mitochondria. Mitochondrial abnormalities in Barth syndrome compromise the development and function of tissues with high energy demand (e.g., heart and skeletal muscles). Biochemically, patients typically present 3-methylglutaconic aciduria, which may be a result of mitochondrial leakage of metabolites from leucine degradation and hypocholesterolaemia; however, disease expressivity and age of onset vary considerably.
TAZ is the only gene whose pathogenic variants are known to cause Barth syndrome.
Barth syndrome is an X-linked genetic condition (a pathogenic variant can be transmitted from mother to son), though the occurrence of de novo pathogenic variants may be relatively high.
The estimated incidence of Barth syndrome is 1 in 300,000–400,000 live births in the US, 1.5 in 1,000,000 live births in France, and 1 in 140,000 live births in England.
Testing for Barth syndrome should be considered for male infants or children with dilated idiopathic cardiomyopathy, neutropenia, 3-methylglutaconic aciduria, abnormal mitochondria within cardiac muscle, and/or idiopathic myopathy association growth retardation.
For management guidelines please refer to:
Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).
Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.
Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.
|Gene||Transcript reference||Sequencing analysis||Deletion/Duplication analysis|