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

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Novel GFM2 variants associated with early-onset neurological presentations of mitochondrial disease and impaired expression of OXPHOS subunits. / Glasgow, Ruth I C; Thompson, Kyle; Barbosa, Inês A; He, Langping; Alston, Charlotte L; Deshpande, Charu; Simpson, Michael A; Morris, Andrew A M; Neu, Axel; Löbel, Ulrike; Hall, Julie; Prokisch, Holger; Haack, Tobias B; Hempel, Maja; McFarland, Robert; Taylor, Robert W.

in: NEUROGENETICS, Jahrgang 18, Nr. 4, 12.2017, S. 227-235.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Glasgow, RIC, Thompson, K, Barbosa, IA, He, L, Alston, CL, Deshpande, C, Simpson, MA, Morris, AAM, Neu, A, Löbel, U, Hall, J, Prokisch, H, Haack, TB, Hempel, M, McFarland, R & Taylor, RW 2017, 'Novel GFM2 variants associated with early-onset neurological presentations of mitochondrial disease and impaired expression of OXPHOS subunits', NEUROGENETICS, Jg. 18, Nr. 4, S. 227-235. https://doi.org/10.1007/s10048-017-0526-4

APA

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. (2017). Novel GFM2 variants associated with early-onset neurological presentations of mitochondrial disease and impaired expression of OXPHOS subunits. NEUROGENETICS, 18(4), 227-235. https://doi.org/10.1007/s10048-017-0526-4

Vancouver

Glasgow RIC, Thompson K, Barbosa IA, He L, Alston CL, Deshpande C et al. Novel GFM2 variants associated with early-onset neurological presentations of mitochondrial disease and impaired expression of OXPHOS subunits. NEUROGENETICS. 2017 Dez;18(4):227-235. https://doi.org/10.1007/s10048-017-0526-4

Bibtex

@article{4dcc642b114c4d91b26b55a4c4ef0432,
title = "Novel GFM2 variants associated with early-onset neurological presentations of mitochondrial disease and impaired expression of OXPHOS subunits",
abstract = "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.",
keywords = "Journal Article",
author = "Glasgow, {Ruth I C} and Kyle Thompson and Barbosa, {In{\^e}s A} and Langping He and Alston, {Charlotte L} and Charu Deshpande and Simpson, {Michael A} and Morris, {Andrew A M} and Axel Neu and Ulrike L{\"o}bel and Julie Hall and Holger Prokisch and Haack, {Tobias B} and Maja Hempel and Robert McFarland and Taylor, {Robert W}",
year = "2017",
month = dec,
doi = "10.1007/s10048-017-0526-4",
language = "English",
volume = "18",
pages = "227--235",
journal = "NEUROGENETICS",
issn = "1364-6745",
publisher = "Springer",
number = "4",

}

RIS

TY - JOUR

T1 - Novel GFM2 variants associated with early-onset neurological presentations of mitochondrial disease and impaired expression of OXPHOS subunits

AU - Glasgow, Ruth I C

AU - Thompson, Kyle

AU - Barbosa, Inês A

AU - He, Langping

AU - Alston, Charlotte L

AU - Deshpande, Charu

AU - Simpson, Michael A

AU - Morris, Andrew A M

AU - Neu, Axel

AU - Löbel, Ulrike

AU - Hall, Julie

AU - Prokisch, Holger

AU - Haack, Tobias B

AU - Hempel, Maja

AU - McFarland, Robert

AU - Taylor, Robert W

PY - 2017/12

Y1 - 2017/12

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1007/s10048-017-0526-4

DO - 10.1007/s10048-017-0526-4

M3 - SCORING: Journal article

C2 - 29075935

VL - 18

SP - 227

EP - 235

JO - NEUROGENETICS

JF - NEUROGENETICS

SN - 1364-6745

IS - 4

ER -