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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 möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Developmental Delay ; Gfm2 ; Mitochondrial Disease ; Mitochondrial Translation ; Wes; Transfer-rna-synthetases; Mutations; Sequence; Genome
ISSN (print) / ISBN 1364-6745
e-ISSN 1364-6753
Zeitschrift Neurogenetics
Quellenangaben Band: 18, Heft: 4, Seiten: 1-9 Artikelnummer: , Supplement: ,
Verlag Springer
Verlagsort New York
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Human Genetics (IHG)