A novel X-linked gene, G4.5. is responsible for Barth syndrome

Bione, Silvia; D’Adamo, Patrizia; Maestrini, Elena; Gedeon, Agi; Bolhuis, P. A.; Toniolo, Daniela

doi:10.1038/ng0496-385

Cited by 702 publications

(496 citation statements)

References 9 publications

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“…In the presence of symptoms suggestive for metabolic disorder (gastrointestinal, neurological involvement, failure to thrive, psychomotor delay, hepato-splenomegaly, cardiac anomalies) and with consistently altered first level investigation (abnormal liver function tests, hypoglycemia, metabolic acidosis) the patient needs to be referred to a Metabolic Disease Reference Center where specific biochemical (urinary organic acid and serum tyrosine) or molecular analyses can be performed (G6PT activity on liver tissue and TAZ gene analysis for Glicogenosis Ib and Barth Syndrome, respectively) [35][36][37][38][39] (Table VII) …”

Section: (Eo 9 A)mentioning

confidence: 99%

Congenital and acquired neutropenia consensus guidelines on diagnosis from the Neutropenia Committee of the Marrow Failure Syndrome Group of the AIEOP (Associazione Italiana Emato‐Oncologia Pediatrica)

Fioredda

Calvillo

Bonanomi

et al. 2011

Pediatric Blood & Cancer

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Congenital and acquired neutropenia are rare disorders whose frequency in pediatric age may be underestimated due to remarkable differences in definition or misdiagnosed because of the lack of common practice guidelines. Neutropenia Committee of the Marrow Failure Syndrome Group (MFSG) of the AIEOP (Associazione Italiana Emato‐Oncologia Pediatrica) elaborated this document following design and methodology formerly approved by the AIEOP board. The panel of experts reviewed the literature on the topic and participated in a conference producing a document which includes a classification of neutropenia and a comprehensive guideline on diagnosis of neutropenia. Pediatr Blood Cancer 2011;57:10–17. © 2011 Wiley‐Liss, Inc.

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Section: (Eo 9 A)mentioning

confidence: 99%

Congenital and acquired neutropenia consensus guidelines on diagnosis from the Neutropenia Committee of the Marrow Failure Syndrome Group of the AIEOP (Associazione Italiana Emato‐Oncologia Pediatrica)

Fioredda

Calvillo

Bonanomi

et al. 2011

Pediatric Blood & Cancer

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“…This X-linked genetic disorder is due to mutations in the tafazzin gene (TAZ) located on region Xq28 [22]. Analyses of the CL profile of different tissues obtained from Barth syndrome patients revealed a decrease in CL and an increase in MLCL and sequence alignments of TAZ showed homology with the glycerolipid acyltransferase family [23][24][25].…”

Section: Cardiolipin Synthesismentioning

confidence: 99%

Cardiolipin: Setting the beat of apoptosis

2007

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Cardiolipin (CL) is a mitochondria-specific phospholipid which is known to be intimately linked with the mitochondrial bioenergetic machinery. Accumulating evidence now suggests that this unique lipid also has active roles in several of the mitochondria-dependant steps of apoptosis. CL is closely associated with cytochrome c at the outer leaflet of the mitochondrial inner membrane. This interaction makes the process of cytochrome c release from mitochondria more complex than previously assumed, requiring more than pore formation in the mitochondrial outer membrane. While CL peroxidation could be crucial for enabling cytochrome c dissociation from the mitochondrial inner membrane, cytochrome c itself catalyzes CL peroxidation. Moreover, peroxy-CL directly activates the release of cytochrome c and other apoptogenic factors from the mitochondria. CL is also directly involved in mitochondrial outer membrane permeabilization by enabling docking and activation of proapoptotic Bcl-2 proteins. It appears therefore that CL has multiple roles in apoptosis and that CL metabolism contributes to the complexity of the apoptotic process.

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“…The disease is often fatal in infancy and early childhood because of cardiac failure and bacterial infections (Barth et al, 2004). Bione et al (1996) identified the gene responsible, termed Tafazzin (TAZ), and localized it to region q28 on the X chromosome. Sequence analyses demonstrate that the Taz protein is highly conserved from yeast to man and that it displays sequence similarity to acyltransferases that participate in the metabolism of phospholipids (Neuwald, 1997).…”

Section: Introductionmentioning

confidence: 99%

Taz1, an Outer Mitochondrial Membrane Protein, Affects Stability and Assembly of Inner Membrane Protein Complexes: Implications for Barth Syndrome

Brandner

Mick

Frazier

et al. 2005

MBoC

190

150

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The Saccharomyces cerevisiae Taz1 protein is the orthologue of human Tafazzin, a protein that when inactive causes Barth Syndrome (BTHS), a severe inherited X-linked disease. Taz1 is a mitochondrial acyltransferase involved in the remodeling of cardiolipin. We show that Taz1 is an outer mitochondrial membrane protein exposed to the intermembrane space (IMS). Transport of Taz1 into mitochondria depends on the receptor Tom5 of the translocase of the outer membrane (TOM complex) and the small Tim proteins of the IMS, but is independent of the sorting and assembly complex (SAM). TAZ1 deletion in yeast leads to growth defects on nonfermentable carbon sources, indicative of a defect in respiration. Because cardiolipin has been proposed to stabilize supercomplexes of the respiratory chain complexes III and IV, we assess supercomplexes in taz1⌬ mitochondria and show that these are destabilized in taz1⌬ mitochondria. This leads to a selective release of a complex IV monomer from the III 2 IV 2 supercomplex. In addition, assembly analyses of newly imported subunits into complex IV show that incorporation of the complex IV monomer into supercomplexes is affected in taz1⌬ mitochondria. We conclude that inactivation of Taz1 affects both assembly and stability of respiratory chain complexes in the inner membrane of mitochondria. INTRODUCTIONBarth Syndrome is an X-linked recessive disorder that is characterized by cardioskeletal myopathy, neutropenia, increased urine levels of 3-methylglutaconic acid, abnormal mitochondria, and respiratory chain dysfunction (Barth et al., 1983(Barth et al., , 1996Kelley et al., 1991;D'Adamo et al., 1997). The disease is often fatal in infancy and early childhood because of cardiac failure and bacterial infections (Barth et al., 2004). Bione et al. (1996) identified the gene responsible, termed Tafazzin (TAZ), and localized it to region q28 on the X chromosome. Sequence analyses demonstrate that the Taz protein is highly conserved from yeast to man and that it displays sequence similarity to acyltransferases that participate in the metabolism of phospholipids (Neuwald, 1997). Phospholipid analyses of fibroblasts from patients and yeast taz1⌬ mutant cells show reduced cardiolipin levels and an altered acyl chain composition (Vreken et al., 2000;Vaz et al., 2003;Xu et al., 2003;Gu et al., 2004).Cardiolipin is formed by two glycerol-linked phosphatidyl moieties. The four acyl side chains are usually monoand di-unsaturated fatty acids in higher eukaryotes. Remodeling of cardiolipin through a cycle of deacylation and successive reacylation leads to the final and specific acyl composition. In heart and skeletal muscle mitochondria the tetralinoleoyl species predominates Xu et al., 2003;Hatch, 2004). Cardiolipin is primarily found in the mitochondrial membranes of eukaryotes (Hoch, 1992) and the bacterial cytoplasmic membrane. Although the molecular function of cardiolipin is still unclear, several studies have suggested that it is required for the proper function of some proteins and protein complexe...

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A novel X-linked gene, G4.5. is responsible for Barth syndrome

Cited by 702 publications

References 9 publications

Congenital and acquired neutropenia consensus guidelines on diagnosis from the Neutropenia Committee of the Marrow Failure Syndrome Group of the AIEOP (Associazione Italiana Emato‐Oncologia Pediatrica)

Congenital and acquired neutropenia consensus guidelines on diagnosis from the Neutropenia Committee of the Marrow Failure Syndrome Group of the AIEOP (Associazione Italiana Emato‐Oncologia Pediatrica)

Cardiolipin: Setting the beat of apoptosis

Taz1, an Outer Mitochondrial Membrane Protein, Affects Stability and Assembly of Inner Membrane Protein Complexes: Implications for Barth Syndrome

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