PuSH - Publication Server of Helmholtz Zentrum München: Novel <em>GFM2 </em>variants associated with early-onset neurological presentations of mitochondrial disease and impaired expression of OXPHOS subunits.

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... Journal

... Publication Type

... Research Data

... Publication Year

Publication overview

Support & Contact

Contact persons

Help

Data protection

Glasgow, R.I.C.* ; Thompson, K.* ; Barbosa, I.A.* ; He, L.* ; Alston, C.L.* ; Deshpande, C.* ; Simpson, M.A.* ; Morris, A.A.M.* ; Neu, A.* ; Löbel, U.* ; Hall, J.* ; Prokisch, H. ; Haack, T.B.* ; Hempel, M.* ; McFarland, R.* ; Taylor, R.W.*

Novel GFM2 variants associated with early-onset neurological presentations of mitochondrial disease and impaired expression of OXPHOS subunits.

Neurogenetics 18, 1-9 (2017)

DOI

PMC

Open Access Green as soon as Postprint is submitted to ZB.

Abstract
Metrics
Extra information

Mitochondrial diseases are characterised by clinical, molecular and functional heterogeneity, reflecting their bi-genomic control. The nuclear gene GFM2 encodes mtEFG2, a protein with an essential role during the termination stage of mitochondrial translation. We present here two unrelated patients harbouring different and previously unreported compound heterozygous (c.569G > A, p.(Arg190Gln); c.636delA, p.(Glu213Argfs*3)) and homozygous (c.275A > C, p.(Tyr92Ser)) recessive variants in GFM2 identified by whole exome sequencing (WES) together with histochemical and biochemical findings to support the diagnoses of pathological GFM2 variants in each case. Both patients presented similarly in early childhood with global developmental delay, raised CSF lactate and abnormalities on cranial MRI. Sanger sequencing of familial samples confirmed the segregation of bi-allelic GFM2 variants with disease, while investigations into steady-state mitochondrial protein levels revealed respiratory chain subunit defects and loss of mtEFG2 protein in muscle. These data demonstrate the effects of defective mtEFG2 function, caused by previously unreported variants, confirming pathogenicity and expanding the clinical phenotypes associated with GFM2 variants.

Altmetric

Additional Metrics?

[➜Log in]

Edit extra informations Login

Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Developmental Delay ; Gfm2 ; Mitochondrial Disease ; Mitochondrial Translation ; Wes; Transfer-rna-synthetases; Mutations; Sequence; Genome

ISSN (print) / ISBN 1364-6745

e-ISSN 1364-6753

Journal Neurogenetics

Quellenangaben Volume: 18, Issue: 4, Pages: 1-9

Publisher Springer

Publishing Place New York

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Human Genetics (IHG)