RT Journal Article
T1 Identification of a Novel Variant in EARS2 Associated with a Severe Clinical Phenotype Expands the Clinical Spectrum of LTBL
A1 Barbosa Gouveia, Sofia
A1 González Vioque, Emiliano
A1 Hermida Ameijeiras, Álvaro
A1 Unceta Suárez, María
A1 Martínez González, María Jesús
A1 Borges, Filipa
A1 Wintjes, Liesbeth
A1 Kappen, Antonia
A1 Rodenburg, Richard
A1 Couce Pico, María Luz
K1 Mitochondrial disorders
K1 Aminoacyl-tRNA synthetases
K1 EARS2
K1 LTBL
AB The EARS2 nuclear gene encodes mitochondrial glutamyl-tRNA synthetase, a member of the class I family of aminoacyl-tRNA synthetases (aaRSs) that plays a crucial role in mitochondrial protein biosynthesis by catalyzing the charging of glutamate to mitochondrial tRNA(Glu). Pathogenic EARS2 variants have been associated with a rare mitochondrial disorder known as leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL). The targeted sequencing of 150 nuclear genes encoding respiratory chain complex subunits and proteins implicated in the oxidative phosphorylation (OXPHOS) function was performed. The oxygen consumption rate (OCR), and the extracellular acidification rate (ECAR), were measured. The enzymatic activities of Complexes I-V were analyzed spectrophotometrically. We describe a patient carrying two heterozygous EARS2 variants, c.376C>T (p.Gln126*) and c.670G>A (p.Gly224Ser), with infantile-onset disease and a severe clinical presentation. We demonstrate a clear defect in mitochondrial function in the patient’s fibroblasts, suggesting the molecular mechanism underlying the pathogenicity of these EARS2 variants. Experimental validation using patient-derived fibroblasts allowed an accurate characterization of the disease-causing variants, and by comparing our patient’s clinical presentation with that of previously reported cases, new clinical and radiological features of LTBL were identified, expanding the clinical spectrum of this disease
PB MDPI
YR 2020
FD 2020
LK http://hdl.handle.net/10347/23868
UL http://hdl.handle.net/10347/23868
LA eng
NO Barbosa-Gouveia, S.; González-Vioque, E.; Hermida, Á.; Suarez, M.U.; Martínez-González, M.J.; Borges, F.; Wintjes, L.; Kappen, A.; Rodenburg, R.; Couce, M.-L. Identification of a Novel Variant in EARS2 Associated with a Severe Clinical Phenotype Expands the Clinical Spectrum of LTBL. Genes 2020, 11, 1028
NO This study was supported with a competitive PhD grant from a pre-Doctoral scholarship for research groups of the Health Research Institute of Santiago (IDIS)
DS Minerva
RD 27 abr 2026