Neonatal, Lethal Noncompaction of the Left Ventricular Myocardium Is Allelic with Barth Syndrome

Bleyl, Steven B.; Mumford, Brian R.; Thompson, Victor; Carey, John C.; Pysher, Theodore J.; Chin, Thomas K.; Ward, Kenneth

doi:10.1086/514879

Cited by 265 publications

(165 citation statements)

References 13 publications

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“…LVNC can occur in patients with malformation syndromes, including velocardiofacial syndrome (Madan et al 2010), Sotos syndrome , as well as states of aneuploidy and mosaicism (Beken et al 2011;McMahon et al 2005;Sellars et al 2011;Wang et al 2007). Furthermore, LVNC has been reported in association with several distinct inborn errors of metabolism (IEM) including Barth syndrome (Bleyl et al 1997 (Finsterer et al 2002); mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke (MELAS) syndrome as well as less well-defined mitochondriopathies (Finsterer et al 2006;St€ ollberger et al 1999). In at least one case, isolated LVNC has manifested as fetal hydrops (Richards et al 2009).…”

Section: Discussionmentioning

confidence: 99%

Noncompaction of the Ventricular Myocardium and Hydrops Fetalis in Cobalamin C Disease

Tanpaiboon

Sloan

Callahan³

et al. 2012

JIMD Reports

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Cobalamin C disease (cblC), a form of combined methylmalonic acidemia and hyperhomocysteinemia caused by mutations in the MMACHC gene, may be the most common inborn error of intracellular cobalamin metabolism. The clinical manifestations of cblC disease are diverse and range from intrauterine growth retardation to adult onset neurological disease. The occurrence of structural heart defects appears to be increased in cblC patients and may be related to the function of the MMACHC enzyme during cardiac embryogenesis, a concept supported by the observation that Mmachc is expressed in the bulbis cordis of the developing mouse heart. Here we report an infant who presented with hydrops fetalis, ventricular dysfunction, and echocardiographic evidence of LVNC, a rare congenital cardiomyopathy. Metabolic evaluations, complementation studies, and mutation analysis confirmed the diagnosis of cblC disease. These findings highlight an intrauterine cardiac phenotype that can be displayed in cblC disease in association with nonimmune hydrops.

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Section: Discussionmentioning

confidence: 99%

Noncompaction of the Ventricular Myocardium and Hydrops Fetalis in Cobalamin C Disease

Tanpaiboon

Sloan

Callahan³

et al. 2012

JIMD Reports

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“…We analyzed G4.5 in both men with isolated DCM and found no mutations. Ichida et al (2001) and Bleyl et al (1997) reported G4.5 mutations in some of their patients with left ventricular noncompaction (LVNC). One could hypothesize that LVNC patients with G4.5 mutations would have the mitochondrial changes of our current patients, whereas LVNC patients lacking G4.5 mutations would not.…”

Section: Discussionmentioning

confidence: 99%

“…lished missense mutations, 7 occur in these motifs. Mutations V183G and G197E have been found repeatedly (Bleyl et al, 1997;Cantlay et al, 1999;D'Adamo et al, 1997;Ichida et al, 2001;Johnston et al, 1997;Neuwald, 1997). The significant clustering of over one-half the reported disease-causing mutations in putative acyltransferase motifs (p Ͻ 0.022, 2 test) may reveal regions of the tafazzin protein critical for its function.…”

Section: Mutations In Gene G45mentioning

confidence: 99%

Infantile Dilated X-Linked Cardiomyopathy, G4.5 Mutations, Altered Lipids, and Ultrastructural Malformations of Mitochondria in Heart, Liver, and Skeletal Muscle

Bissler

Tsoras

Göring

et al. 2002

Laboratory Investigation

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SUMMARY:Mutations in the Xq28 gene G4.5 lead to dilated cardiomyopathy (DCM). Differential splicing of G4.5 results in a family of proteins called "tafazzins" with homology to acyltransferases. These enzymes assemble fatty acids into membrane lipids. We sequenced G4.5 in two kindreds with X-linked DCM and in two unrelated men, one with idiopathic DCM and the other with DCM of arrhythmogenic right ventricular dysplasia. We examined the ultrastructure of heart, liver, and muscle biopsy specimens in these three DCM types; we used gas chromatography to compare fatty acid composition in heart, liver, and muscle autopsy specimens of two patients of kindred 1 with that of controls. In X-linked DCM, G4.5 had a stop codon (E188X), a nonsense mutation, in kindred 1 and an amino acid substitution (G240R), a missense mutation, in kindred 2. In the two men with isolated DCM, G4.5 was not mutated. Ultrastructural mitochondrial malformations were present in the biopsy tissues of the patients with DCM. Cardiac biopsy specimens of both kindreds with X-linked DCM exhibited greatly enlarged mitochondria with large bundles of stacked, compacted, disarrayed cristae that differed from those of the two types of isolated DCM. Autopsy tissue of patients with X-linked DCM had decreased unsaturated and increased saturated fatty acid concentrations. Seven of 13 published G4.5 missense mutations, including the one presented here, occur in acyltransferase motifs. Impaired acyltransferase function could result in increased fatty acid saturation that would decrease membrane fluidity. Mitochondrial membrane proliferation may be an attempt to compensate for impaired function of acyltransferase. Cardiac ultrastructure separates X-linked DCM with G4.5 mutations from the two types of isolated DCM without G4.5 mutations. Electron microscopy of promptly fixed myocardial biopsy specimens has a role in defining the differential diagnosis of DCM. Mutational analysis of the G4.5 gene also serves this purpose. (Lab Invest 2002, 82:335-344).

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“…Some variants showed both sporadic and familial inheritance patterns in different studies (p.G197R/ TAZ ) (Bleyl et al. 1997b). …”

Section: Resultsmentioning

confidence: 99%

The pathogenicity of genetic variants previously associated with left ventricular non‐compaction

Abbasi

Jabbari

et al. 2015

Molec Gen & Gen Med

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BackgroundLeft ventricular non‐compaction (LVNC) is a rare cardiomyopathy. Many genetic variants have been associated with LVNC. However, the number of the previous LVNC‐associated variants that are common in the background population remains unknown. The aim of this study was to provide an updated list of previously reported LVNC‐associated variants with biologic description and investigate the prevalence of LVNC variants in healthy general population to find false‐positive LVNC‐associated variants.Methods and ResultsThe Human Gene Mutation Database and PubMed were systematically searched to identify all previously reported LVNC‐associated variants. Thereafter, the Exome Sequencing Project (ESP) and the Exome Aggregation Consortium (ExAC), that both represent the background population, was searched for all variants. Four in silico prediction tools were assessed to determine the functional effects of these variants. The prediction results of those identified in the ESP and ExAC and those not identified in the ESP and ExAC were compared. In 12 genes, 60 LVNC‐associated missense/nonsense variants were identified. MYH7 was the predominant gene, encompassing 24 of the 60 LVNC‐associated variants. The ESP only harbored nine and ExAC harbored 18 of the 60 LVNC‐associated variants. In total, eight out of nine ESP‐positive variants overlapped with the 18 variants identified in ExAC database.ConclusionsIn this article, we identified 9 ESP‐positive and 18 ExAC‐positive variants of 60 previously reported LVNC‐associated variants, suggesting that these variants are not necessarily the monogenic cause of LVNC.

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Neonatal, Lethal Noncompaction of the Left Ventricular Myocardium Is Allelic with Barth Syndrome

Cited by 265 publications

References 13 publications

Noncompaction of the Ventricular Myocardium and Hydrops Fetalis in Cobalamin C Disease

Noncompaction of the Ventricular Myocardium and Hydrops Fetalis in Cobalamin C Disease

Infantile Dilated X-Linked Cardiomyopathy, G4.5 Mutations, Altered Lipids, and Ultrastructural Malformations of Mitochondria in Heart, Liver, and Skeletal Muscle

The pathogenicity of genetic variants previously associated with left ventricular non‐compaction

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