Gonadal mosaicism of a TAZ (G4.5) mutation in a Japanese family with Barth syndrome and left ventricular noncompaction

Chang, Bo; Momoi, Nobuo; Shan, Lishen; Mitomo, M; Aoyagi, Yoshimichi; Endo, Kisei; Takeda, Izumi; Chen, Rui; Xing, Yanlin; Yu, Xiao‐Juan; Watanabe, Sayaka; Yoshida, Taketoshi; Kanegane, Hirokazu; Tsubata, Shinichi; Bowles, Neil E.; Ichida, Fukiko; Miyawaki, Toshio

doi:10.1016/j.ymgme.2010.02.021

Cited by 19 publications

(12 citation statements)

References 42 publications

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“…Disease-causing mutations have been found in all exons of the TAZ gene [4,40,41]. The TAZ mutations in our cohort have been reported in previous studies [7,14,22-27] and/or in the BSF TAZ mutations database [28].…”

Section: Discussionmentioning

confidence: 54%

Natural history of Barth syndrome: a national cohort study of 22 patients

Rigaud

Lèbre

Touraine

et al. 2013

Orphanet J Rare Dis

110

151

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BackgroundThis study describes the natural history of Barth syndrome (BTHS).MethodsThe medical records of all patients with BTHS living in France were identified in multiple sources and reviewed.ResultsWe identified 16 BTHS pedigrees that included 22 patients. TAZ mutations were observed in 15 pedigrees. The estimated incidence of BTHS was 1.5 cases per million births (95%CI: 0.2–2.3). The median age at presentation was 3.1 weeks (range, 0–1.4 years), and the median age at last follow-up was 4.75 years (range, 3–15 years). Eleven patients died at a median age of 5.1 months; 9 deaths were related to cardiomyopathy and 2 to sepsis. The 5-year survival rate was 51%, and no deaths were observed in patients ≥3 years. Fourteen patients presented with cardiomyopathy, and cardiomyopathy was documented in 20 during follow-up. Left ventricular systolic function was very poor during the first year of life and tended to normalize over time. Nineteen patients had neutropenia. Metabolic investigations revealed inconstant moderate 3-methylglutaconic aciduria and plasma arginine levels that were reduced or in the low-normal range. Survival correlated with two prognostic factors: severe neutropenia at diagnosis (<0.5 × 109/L) and birth year. Specifically, the survival rate was 70% for patients born after 2000 and 20% for those born before 2000.ConclusionsThis survey found that BTHS outcome was affected by cardiac events and by a risk of infection that was related to neutropenia. Modern management of heart failure and prevention of infection in infancy may improve the survival of patients with BTHS without the need for heart transplantation.

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Section: Discussionmentioning

confidence: 54%

Natural history of Barth syndrome: a national cohort study of 22 patients

Rigaud

Lèbre

Touraine

et al. 2013

Orphanet J Rare Dis

110

151

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“…Gonadal mosaicism has also been documented [18], raising the small possibility that a woman who does not herself carry mutations in her somatic DNA may have more than one affected boy.…”

Section: Reviewmentioning

confidence: 99%

Barth syndrome

Clarke

Bowron

Gonzalez

et al. 2013

Orphanet J Rare Dis

296

392

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First described in 1983, Barth syndrome (BTHS) is widely regarded as a rare X-linked genetic disease characterised by cardiomyopathy (CM), skeletal myopathy, growth delay, neutropenia and increased urinary excretion of 3-methylglutaconic acid (3-MGCA). Fewer than 200 living males are known worldwide, but evidence is accumulating that the disorder is substantially under-diagnosed. Clinical features include variable combinations of the following wide spectrum: dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), endocardial fibroelastosis (EFE), left ventricular non-compaction (LVNC), ventricular arrhythmia, sudden cardiac death, prolonged QTc interval, delayed motor milestones, proximal myopathy, lethargy and fatigue, neutropenia (absent to severe; persistent, intermittent or perfectly cyclical), compensatory monocytosis, recurrent bacterial infection, hypoglycaemia, lactic acidosis, growth and pubertal delay, feeding problems, failure to thrive, episodic diarrhoea, characteristic facies, and X-linked family history. Historically regarded as a cardiac disease, BTHS is now considered a multi-system disorder which may be first seen by many different specialists or generalists. Phenotypic breadth and variability present a major challenge to the diagnostician: some children with BTHS have never been neutropenic, whereas others lack increased 3-MGCA and a minority has occult or absent CM. Furthermore, BTHS was first described in 2010 as an unrecognised cause of fetal death. Disabling mutations or deletions of the tafazzin (TAZ) gene, located at Xq28, cause the disorder by reducing remodeling of cardiolipin, a principal phospholipid of the inner mitochondrial membrane. A definitive biochemical test, based on detecting abnormal ratios of different cardiolipin species, was first described in 2008. Key areas of differential diagnosis include metabolic and viral cardiomyopathies, mitochondrial diseases, and many causes of neutropenia and recurrent male miscarriage and stillbirth. Cardiolipin testing and TAZ sequencing now provide relatively rapid diagnostic testing, both prospectively and retrospectively, from a range of fresh or stored tissues, blood or neonatal bloodspots. TAZ sequencing also allows female carrier detection and antenatal screening. Management of BTHS includes medical therapy of CM, cardiac transplantation (in 14% of patients), antibiotic prophylaxis and granulocyte colony-stimulating factor (G-CSF) therapy. Multidisciplinary teams/clinics are essential for minimising hospital attendances and allowing many more individuals with BTHS to live into adulthood.

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“…A complete list of reported mutations is maintained and updated by the Barth Syndrome Foundation (http://www.barth-sydrome.org). Less than 20% of boys carry de novo mutations not identified in maternal somatic DNA but gonadal mosacisim has been reported [Chang et al, 2010]. There are no reported genotype/phenotype correlations in BTHS and it is increasingly recognized that there may be significant intrafamilial phenotypic variability [Ronvelia et al, 2012].…”

Section: Geneticsmentioning

confidence: 99%

Barth syndrome

Jefferies¹

2013

American J of Med Genetics Pt C

110

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Barth syndrome (BTHS) is an X-linked recessive disorder that is typically characterized by cardiomyopathy (CMP), skeletal myopathy, growth retardation, neutropenia, and increased urinary levels of 3-methylglutaconic acid (3-MGCA). There may be a wide variability of phenotypes amongst BTHS patients with some exhibiting some or all of these findings. BTHS was first described as a disease of the mitochondria resulting in neutropenia as well as skeletal and cardiac myopathies. Over the past few years, a greater understanding of BTHS has developed related to the underlying genetic mechanisms responsible for the disease. Mutations in the TAZ gene on chromosome Xq28, also known as G4.5, are responsible for the BTHS phenotype resulting in a loss-of-function in the protein product tafazzin. Clinical management of BTHS has also seen improvement. Patients with neutropenia are susceptible to life-threatening bacterial infections with sepsis being a significant concern for possible morbidity and mortality. Increasingly, BTHS patients are suffering from heart failure secondary to their CMP. Left ventricular noncompaction (LVNC) and dilated CMP are the most common cardiac phenotypes reported and can lead to symptoms of heart failure as well as ventricular arrhythmias. Expanded treatment options for end-stage myocardial dysfunction now offer an opportunity to change the natural history for these patients. Herein, we will provide a current review of the genetic and molecular basis of BTHS, the clinical features and management of BTHS, and potential future directions for therapeutic strategies. © 2013 Wiley Periodicals, Inc.

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Gonadal mosaicism of a TAZ (G4.5) mutation in a Japanese family with Barth syndrome and left ventricular noncompaction

Cited by 19 publications

References 42 publications

Natural history of Barth syndrome: a national cohort study of 22 patients

Natural history of Barth syndrome: a national cohort study of 22 patients

Barth syndrome

Barth syndrome

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