Transition from Leigh syndrome to MELAS syndrome in a patient with heteroplasmic MT-ND3 m.10158T&gt;C

Kori, Atsuko; Hori, Ikumi; Tanaka, Tatsushi; Aoyama, Kohei; Ito, Koichi; Hattori, Ayako; Ban, Kyoko; Okazaki, Yasushi; Murayama, Kei; Saitoh, Shinji

doi:10.1016/j.braindev.2019.05.006

Cited by 12 publications

(6 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Most cases of the 10191T>C MT-ND3 mutation have a clinical presentation of LS, MELAS/LS, or nonspecific encephalopathy (12). Likewise, MELAS, LS, or MELAS/LS overlap syndromes were previously reported in patients with the m.10158T>C mutation (13,14). The most common phenotype associated with m.10197 G>A was LS or LS-like syndrome, followed by dystonia or LHON and dystonia (LDYT), whereas MELAS/LS was rarely reported (15).…”

Section: Discussionmentioning

confidence: 99%

MELAS/LS Overlap Syndrome Associated With Mitochondrial DNA Mutations: Clinical, Genetic, and Radiological Studies

et al. 2021

View full text Add to dashboard Cite

Introduction: Mitochondrial diseases are characterized by considerable clinical and genetic heterogeneity. Mitochondrial encephalomyopathy with lactate acidosis and stroke-like episodes (MELAS) and Leigh syndrome (LS) are both established mitochondrial syndromes; sometimes they can overlap.Methods: A retrospective observational cohort study was done to analyze the clinical manifestations, biochemical findings, neuroimaging and genetic data, and disease outcomes of 14 patients with identified MELAS/LS overlap syndrome.Results: A total of 14 patients, 9 males and 5 females, were enrolled. The median age at onset was 14 years, while the average age was 12.6 years. As for clinical features in concordance with MELAS, the top three most common symptoms were seizures, cognitive impairment, and stroke-like episodes (SLE). Brain atrophy was present in seven patients. As for the clinical hallmarks of LS, the top three most common symptoms were ataxia, spastic paraplegia, and bulbar palsy. Patients presented with individual syndrome or overlap syndromes with similar frequency, and the prognosis did not seem to be related to the initial presentation. Thirteen patients were identified with MTND mutations, among which m.13513G>A mutation in the MT-ND5 gene was the most common. Only one patient with m.8344A>G mutation of MTTK gene was found.Discussion: Our study demonstrated that MTND genes are important mutation hot spots in MELAS/LS overlap syndrome. The follow-up is very important for the final diagnosis of overlap syndrome.

show abstract

Section: Discussionmentioning

confidence: 99%

MELAS/LS Overlap Syndrome Associated With Mitochondrial DNA Mutations: Clinical, Genetic, and Radiological Studies

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Phenotypes related to these diseases usually do not present at the prenatal stage, but these incidental findings had clinical significance for pregnancy management and postnatal treatment. Of note, despite the low mutation load, the MT‐ND3 gene mutation detected in Case 38 was known to cause severe progressive neurodegenerative disease 30 , and since this variant occurred de novo , there was a risk of developing the disease postnatally owing to mitochondrial DNA heteroplasmy and tissue specificity. Compared with previous pES studies, the incorporation of mitochondrial genome in pES testing provided more comprehensive genetic information for the parents in our study, but it would definitely increase the complexity of data interpretation and genetic counseling in the clinical setting.…”

Section: Discussionmentioning

confidence: 99%

Utility of trio‐based prenatal exome sequencing incorporating splice‐site and mitochondrial genome assessment in pregnancies with fetal ultrasound anomalies: prospective cohort study

Zhu

Gao

Wang

et al. 2022

Ultrasound in Obstet & Gyne

View full text Add to dashboard Cite

What are the novel findings of this work?Trio-based prenatal exome sequencing (pES) had an incremental yield of 31% in ongoing pregnancies with fetal ultrasound anomalies but undiagnosed by copy-number variant sequencing (CNV-seq). Comprehensive analysis of nuclear exome coding and splicing regions, as well as mitochondrial genome, provided not only diagnostic findings but also incidental findings (in 7.8% cases) that were important for affected families. What are the clinical implications of this work?Trio-based pES is an efficient diagnostic method for families with fetal ultrasound anomalies and normal CNV-seq results. The incidental findings and parental carrier status detected by trio-based pES extend its clinical application, but careful genetic counseling is warranted.

show abstract

“…Eight genes clustered in this function include ND3, EGR1, MMP14, FOSB, HSPA5 (GRP78), SSRT4, TMBD, and ARNTL. All of them contribute to cell metabolism or stress responses 54‐63 . As summarized in Table 2, all except SSRT4 exhibit direct association or contribution to stroke outcome or cerebrovascular function.…”

Section: Discussionmentioning

confidence: 99%

“…All of them contribute to cell metabolism or stress responses. [54][55][56][57][58][59][60][61][62][63] As summarized in Table 2, all except SSRT4 exhibit direct association or contribution to stroke outcome or cerebrovascular function.…”

Section: Discussionmentioning

confidence: 99%

RNA‐Seq analysis of knocking out the neuroprotective proton‐sensitive GPR68 on basal and acute ischemia‐induced transcriptome changes and signaling in mouse brain

2021

View full text Add to dashboard Cite

Brain acid signaling plays important roles in both physiological and disease conditions. One key neuronal metabotropic proton receptor in the brain is GPR68, which contributes to hippocampal long-term potentiation (LTP) and mediates neuroprotection in acidotic and ischemic conditions. Here, to gain greater understanding of GPR68 function in the brain, we performed mRNA-Seq analysis in mice. First, we studied sham-operated animals to determine baseline expression. Compared to wild type (WT), GPR68−/− (KO) brain downregulated genes that are enriched in Gene Ontology (GO) terms of misfolding protein binding, response to organic cyclic compounds, and endoplasmic reticulum chaperone complex. Next, we examined the expression profile following transient middle cerebral artery occlusion (tMCAO). tMCAO-upregulated genes cluster to cytokine/chemokine-related functions and immune responses, while tMCAO-downregulated genes cluster to channel activities and synaptic signaling. For proton-sensitive receptors, tMCAO downregulated ASIC1a and upregulated GPR4 and GPR65, but had no effect on ASIC2, PAC, or GPR68. GPR68 deletion did not alter the expression of these proton receptors, either at baseline or after ischemia. Lastly, we performed GeneVenn analysis of differential genes at baseline and post-tMCAO. Ischemia upregulated the expression of three hemoglobin genes, along with H2-Aa, Ppbp, Siglece, and Tagln, in WT but not in KO. Immunostaining showed that tMCAO-induced hemoglobin localized to neurons. Western blot analysis further showed that hemoglobin induction is GPR68dependent. Together, these data suggest that GPR68 deletion at baseline disrupts chaperone functions and cellular signaling responses and imply a contribution of hemoglobin-mediated antioxidant mechanism to GPR68-dependent neuroprotection in ischemia.

show abstract

Transition from Leigh syndrome to MELAS syndrome in a patient with heteroplasmic MT-ND3 m.10158T>C

Cited by 12 publications

References 10 publications

MELAS/LS Overlap Syndrome Associated With Mitochondrial DNA Mutations: Clinical, Genetic, and Radiological Studies

MELAS/LS Overlap Syndrome Associated With Mitochondrial DNA Mutations: Clinical, Genetic, and Radiological Studies

Utility of trio‐based prenatal exome sequencing incorporating splice‐site and mitochondrial genome assessment in pregnancies with fetal ultrasound anomalies: prospective cohort study

RNA‐Seq analysis of knocking out the neuroprotective proton‐sensitive GPR68 on basal and acute ischemia‐induced transcriptome changes and signaling in mouse brain

Contact Info

Product

Resources

About