Cardiomyopathy in children with mitochondrial disease: Prognosis and genetic background

Imai‐Okazaki, Atsuko; Kishita, Yoshihito; Kohda, Masakazu; Mizuno, Yosuke; Fushimi, Takuya; Matsunaga, Ayako; Yatsuka, Yukiko; Hirata, Tomoko; Harashima, Hiroko; Takeda, Atsuhito; Nakaya, Akihiro; Sakata, Yasushi; Kogaki, Shigetoyo; Ohtake, Akira; Murayama, Kei; Okazaki, Yasushi

doi:10.1016/j.ijcard.2019.01.017

Cited by 37 publications

(31 citation statements)

References 24 publications

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“…The heteroplasmy rates of the m.3243 A > G and m.13513 G > A variations were independently analyzed by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) as described previously 28 .…”

Section: Methodsmentioning

confidence: 99%

A simple method for sequencing the whole human mitochondrial genome directly from samples and its application to genetic testing

Nishimura

Murayama

et al. 2019

Sci Rep

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Next-generation sequencing (NGS) is a revolutionary sequencing technology for analyzing genomes. However, preprocessing methods for mitochondrial DNA (mtDNA) sequencing remain complex, and it is required to develop an authenticated preprocessing method. Here, we developed a simple and easy preprocessing method based on isothermal rolling circle mtDNA amplification using commercially available reagents. Isothermal amplification of mtDNA was successfully performed using both nanoliter quantities of plasma directly and 25 ng of total DNA extracted from blood or tissue samples. Prior to mtDNA amplification, it was necessary to treat the extracted total DNA with Exonuclease V, but it was not required to treat plasma. The NGS libraries generated from the amplified mtDNA provided sequencing coverage of the entire human mitochondrial genome. Furthermore, the sequencing results successfully detected heteroplasmy in patient samples, with called mutations and variants matching those from previous, independent, Sanger sequencing analysis. Additionally, a novel single nucleotide variant was detected in a healthy volunteer. The successful analysis of mtDNA using very small samples from patients is likely to be valuable in clinical medicine, as it could reduce patient discomfort by reducing sampling-associated damage to tissues. Overall, the simple and convenient preprocessing method described herein may facilitate the future development of NGS-based clinical and forensic mtDNA tests.

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Section: Methodsmentioning

confidence: 99%

A simple method for sequencing the whole human mitochondrial genome directly from samples and its application to genetic testing

Nishimura

Murayama

et al. 2019

Sci Rep

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“… 7 These symptoms appear individually or concomitant to other syndromes, which are ignored as common diseases ( Table 1 ). Furthermore, some progress has been made on cardiac manifestations, 3 , 8 as well as complications during pregnancy and perinatal period. 9 This article provides a review of the non-syndromic phenotypes and latest developments in m.3243A> G mutation.…”

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confidence: 99%

The non-syndromic clinical spectrums of mtDNA 3243A>G mutation

Shen

2021

NSJ

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The m.3243A >G mutation in the tRNA Leu )UUR( gene )MT-TL1( of the mitochondrial DNA is the most widely seen pathogenic mtDNA mutation which has major phenotypic variations. The clinical phenotype involves various organs such as the brain and nerves, skeletal muscles, heart, endocrine system, gastrointestinal tract, and skin. Some phenotypes conform to well established syndromes, while most of the symptoms appear individually or concomitant to other syndromes, making identification difficult. Furthermore, some progress has been made on cardiac manifestations as well as complications during pregnancy and perinatal period. This article provides a systematic review of the non-syndromic phenotypes and latest developments in m.3243A>G mutation.

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“…Although the true prevalence of mtDNA-related CM is unknown, based on the prevalence of mtDNA disease and frequency of cardiac manifestations, about 1/10,000–15,000 of the general population is affected [ 7 ]. Furthermore, several studies report different prevalence between pediatric and adult population, with cardiomyopathy estimated to occur in 20–40% of children with MDs [ 16 , 22 , 47 , 48 ].…”

Section: Mitochondrial Cardiomyopathy (Mcm)mentioning

confidence: 99%

Molecular Epidemiology of Mitochondrial Cardiomyopathy: A Search Among Mitochondrial and Nuclear Genes

Mazzaccara

Mirra

Barretta

et al. 2021

IJMS

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Mitochondrial Cardiomyopathy (MCM) is a common manifestation of multi-organ Mitochondrial Diseases (MDs), occasionally present in non-syndromic cases. Diagnosis of MCM is complex because of wide clinical and genetic heterogeneity and requires medical, laboratory, and neuroimaging investigations. Currently, the molecular screening for MCM is fundamental part of MDs management and allows achieving the definitive diagnosis. In this article, we review the current genetic knowledge associated with MDs, focusing on diagnosis of MCM and MDs showing cardiac involvement. We searched for publications on mitochondrial and nuclear genes involved in MCM, mainly focusing on genetic screening based on targeted gene panels for the molecular diagnosis of the MCM, by using Next Generation Sequencing. Here we report twelve case reports, four case-control studies, eleven retrospective studies, and two prospective studies, for a total of twenty-nine papers concerning the evaluation of cardiac manifestations in mitochondrial diseases. From the analysis of published causal mutations, we identified 130 genes to be associated with mitochondrial heart diseases. A large proportion of these genes (34.3%) encode for key proteins involved in the oxidative phosphorylation system (OXPHOS), either as directly OXPHOS subunits (22.8%), and as OXPHOS assembly factors (11.5%). Mutations in several mitochondrial tRNA genes have been also reported in multi-organ or isolated MCM (15.3%). This review highlights the main disease-genes, identified by extensive genetic analysis, which could be included as target genes in next generation panels for the molecular diagnosis of patients with clinical suspect of mitochondrial cardiomyopathies.

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Cardiomyopathy in children with mitochondrial disease: Prognosis and genetic background

Cited by 37 publications

References 24 publications

A simple method for sequencing the whole human mitochondrial genome directly from samples and its application to genetic testing

A simple method for sequencing the whole human mitochondrial genome directly from samples and its application to genetic testing

The non-syndromic clinical spectrums of mtDNA 3243A>G mutation

Molecular Epidemiology of Mitochondrial Cardiomyopathy: A Search Among Mitochondrial and Nuclear Genes

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