Evidence map›Paper›PMID 35252560›Full record

ArticleNeurology. Genetics2022

Novel Pathogenic Sequence Variation m.5789T>C Causes NARP Syndrome and Promotes Formation of Deletions of the Mitochondrial Genome.

Marius Hippen, Gábor Zsurka, Viktoriya Peeva, Judith Machts, Kati Schwiecker, Grazyna Debska-Vielhaber, Rudolf J Wiesner, Stefan Vielhaber, Wolfram S Kunz

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Article in Neurology. Genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 46% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Marius HippenDivision of Neurochemistry (M.H., G.Z., V.P., W.S.K.), Institute of Experimental Epileptology and Cognition Research, University of Bonn; Department of Epileptology (G.Z., W.S.K.), University of Bonn; Center for Behavioral Brain Sciences (CBBS) (J.M.), Magdeburg; Department of Neurology (K.S., G.D.-V., S.V.), University of Magdeburg; and Institute of Vegetative Physiology (R.J.W.), University of Cologne, Germany.
Gábor ZsurkaDivision of Neurochemistry (M.H., G.Z., V.P., W.S.K.), Institute of Experimental Epileptology and Cognition Research, University of Bonn; Department of Epileptology (G.Z., W.S.K.), University of Bonn; Center for Behavioral Brain Sciences (CBBS) (J.M.), Magdeburg; Department of Neurology (K.S., G.D.-V., S.V.), University of Magdeburg; and Institute of Vegetative Physiology (R.J.W.), University of Cologne, Germany.ORCID https://orcid.org/0000-0002-6379-849X
Viktoriya PeevaDivision of Neurochemistry (M.H., G.Z., V.P., W.S.K.), Institute of Experimental Epileptology and Cognition Research, University of Bonn; Department of Epileptology (G.Z., W.S.K.), University of Bonn; Center for Behavioral Brain Sciences (CBBS) (J.M.), Magdeburg; Department of Neurology (K.S., G.D.-V., S.V.), University of Magdeburg; and Institute of Vegetative Physiology (R.J.W.), University of Cologne, Germany.
Judith MachtsDivision of Neurochemistry (M.H., G.Z., V.P., W.S.K.), Institute of Experimental Epileptology and Cognition Research, University of Bonn; Department of Epileptology (G.Z., W.S.K.), University of Bonn; Center for Behavioral Brain Sciences (CBBS) (J.M.), Magdeburg; Department of Neurology (K.S., G.D.-V., S.V.), University of Magdeburg; and Institute of Vegetative Physiology (R.J.W.), University of Cologne, Germany.
Kati SchwieckerDivision of Neurochemistry (M.H., G.Z., V.P., W.S.K.), Institute of Experimental Epileptology and Cognition Research, University of Bonn; Department of Epileptology (G.Z., W.S.K.), University of Bonn; Center for Behavioral Brain Sciences (CBBS) (J.M.), Magdeburg; Department of Neurology (K.S., G.D.-V., S.V.), University of Magdeburg; and Institute of Vegetative Physiology (R.J.W.), University of Cologne, Germany.
Grazyna Debska-VielhaberDivision of Neurochemistry (M.H., G.Z., V.P., W.S.K.), Institute of Experimental Epileptology and Cognition Research, University of Bonn; Department of Epileptology (G.Z., W.S.K.), University of Bonn; Center for Behavioral Brain Sciences (CBBS) (J.M.), Magdeburg; Department of Neurology (K.S., G.D.-V., S.V.), University of Magdeburg; and Institute of Vegetative Physiology (R.J.W.), University of Cologne, Germany.
Rudolf J WiesnerDivision of Neurochemistry (M.H., G.Z., V.P., W.S.K.), Institute of Experimental Epileptology and Cognition Research, University of Bonn; Department of Epileptology (G.Z., W.S.K.), University of Bonn; Center for Behavioral Brain Sciences (CBBS) (J.M.), Magdeburg; Department of Neurology (K.S., G.D.-V., S.V.), University of Magdeburg; and Institute of Vegetative Physiology (R.J.W.), University of Cologne, Germany.
Stefan VielhaberDivision of Neurochemistry (M.H., G.Z., V.P., W.S.K.), Institute of Experimental Epileptology and Cognition Research, University of Bonn; Department of Epileptology (G.Z., W.S.K.), University of Bonn; Center for Behavioral Brain Sciences (CBBS) (J.M.), Magdeburg; Department of Neurology (K.S., G.D.-V., S.V.), University of Magdeburg; and Institute of Vegetative Physiology (R.J.W.), University of Cologne, Germany.
Wolfram S KunzDivision of Neurochemistry (M.H., G.Z., V.P., W.S.K.), Institute of Experimental Epileptology and Cognition Research, University of Bonn; Department of Epileptology (G.Z., W.S.K.), University of Bonn; Center for Behavioral Brain Sciences (CBBS) (J.M.), Magdeburg; Department of Neurology (K.S., G.D.-V., S.V.), University of Magdeburg; and Institute of Vegetative Physiology (R.J.W.), University of Cologne, Germany.ORCID https://orcid.org/0000-0003-1113-3493
Center for Behavioral Brain Sciences · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesWe report the pathogenic sequence variant m.5789T>C in the anticodon stem of the mitochondrial tRNA for cysteine as a novel cause of neuropathy, ataxia, and retinitis pigmentosa (NARP), which is usually associated with pathogenic variants in the

methodsTo address the correlation of oxidative phosphorylation deficiency with mutation loads, we performed genotyping on single laser-dissected skeletal muscle fibers. Stability of the mitochondrial tRNA

resultsThe sequence variant m.5789T>C, originating from the patient's mother, decreases the stability of the mitochondrial tRNA for cysteine by disrupting the anticodon stem, which subsequently leads to a combined oxidative phosphorylation deficiency. In parallel, we observed a prominent cluster of low-abundance somatic deletions with breakpoints in the immediate vicinity of the m.5789T>C variant. Strikingly, all deletion-carrying mitochondrial DNA (mtDNA) species, in which the corresponding nucleotide position was not removed, harbored the mutant allele, and none carried the wild-type allele. DISCUSSION: In addition to providing evidence for the novel association of a tRNA sequence alteration with NARP syndrome, our observations support the hypothesis that single nucleotide changes can lead to increased occurrence of site-specific mtDNA deletions through the formation of an imperfect repeat. This finding might be relevant for understanding mechanisms of deletion generation in the human mitochondrial genome.

Identifiers

PMID35252560
PMCPMC8893589
OpenAlexW4214831538

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.