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Metabolic Brain Disease

, Volume 32, Issue 1, pp 267–270 | Cite as

Neonatal encephalocardiomyopathy caused by mutations in VARS2

  • Fabian Baertling
  • Bader Alhaddad
  • Annette Seibt
  • Sonja Budaeus
  • Thomas Meitinger
  • Tim M. Strom
  • Ertan Mayatepek
  • Jörg Schaper
  • Holger Prokisch
  • Tobias B. Haack
  • Felix Distelmaier
Short Communication

Abstract

VARS2 encodes a mitochondrial aminoacyl-tRNA-synthetase. Mutations in VARS2 have recently been identified as a cause of mitochondrial encephalomyopathy in three individuals. However, clinical information remained scarce. Exome sequencing lead us to identify compound heterozygous pathogenic VARS2 variants in a boy presenting with severe lactic acidosis, hypertrophic cardiomyopathy, epilepsy, and abnormalities on brain imaging including hypoplasia of corpus callosum and cerebellum as well as a massive lactate peak on MR-spectroscopy. Studies in patient-derived fibroblasts confirmed the functional relevance of the identified VARS2 variants. Our report expands the phenotypic spectrum associated with this rare mitochondrial defect, in that VARS2 deficiency may also cause severe neonatal presentations with cardiac involvement and structural brain abnormalities.

Keywords

VARS2 OXPHOS Mitochondrial disease Cardiomyopathy Aminoacyl tRNA synthtetase 

Abbreviations

EEG

electroencephalography

mt-aaRS

mitochondrial aminoacyl-tRNA-synthetases

MRI

magnetic resonance imaging

OXPHOS

oxidative phosphorylation

SDS-PAGE

Sodium dodecyl polyacrylamide gel electrophoresis

MRS

magnetic resonance spectroscopy

Notes

Funding

This project was supported by the BMBF funded German Network for Mitochondrial Disorders (mitoNET #01GM1113C) and by the E-Rare project GENOMIT (01GM1207). TBH was supported by the BMBF through the Juniorverbund in der Systemmedizin “mitOmics” (FKZ 01ZX1405C). FD was supported by a grant of the Forschungskommission of the Medical Faculty of the Heinrich-Heine-University Düsseldorf. FB was supported by a fellowship of the German Research Foundation/Deutsche Forschungsgemeinschaft (BA 5758/1–1).

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Fabian Baertling
    • 1
  • Bader Alhaddad
    • 2
  • Annette Seibt
    • 1
  • Sonja Budaeus
    • 1
  • Thomas Meitinger
    • 2
    • 3
    • 4
  • Tim M. Strom
    • 2
    • 3
  • Ertan Mayatepek
    • 1
  • Jörg Schaper
    • 5
  • Holger Prokisch
    • 2
    • 3
  • Tobias B. Haack
    • 2
    • 3
  • Felix Distelmaier
    • 1
  1. 1.Department of General Pediatrics, Neonatology and Pediatric CardiologyUniversity Children’s Hospital Duesseldorf, Heinrich Heine UniversityDüsseldorfGermany
  2. 2.Institute of Human GeneticsTechnische Universität MünchenMunichGermany
  3. 3.Institute of Human GeneticsHelmholtz Zentrum MünchenNeuherbergGermany
  4. 4.Munich Cluster for Systems Neurology (SyNergy)MunichGermany
  5. 5.Medical Faculty, Department of Diagnostic and Interventional RadiologyUniversity DüsseldorfDüsseldorfGermany

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