Further delineation of a rare recessive encephalomyopathy linked to mutations in <scp>GFER</scp> thanks to data sharing of whole exome sequencing data

Nambot, Sophie; Gavrilov, Dimitar; Thévenon, Julien; Bruel, Ange Line; Bainbridge, Matthew N.; Rio, Marlène; Goizet, Cyril; Rötig, Agnès; Jaeken, Jacques; Niu, Nifang; Xia, Fan; Vital, Anne; Houcinat, Nada; Mochel, Fanny; Kuentz, Paul; Lehalle, Daphné; Duffourd, Yannis; Rivière, Jean Baptiste; Thauvin‐Robinet, Christel; Beaudet, Arthur L.; Faivre, Laurence

doi:10.1111/cge.12985

Cited by 21 publications

(17 citation statements)

References 35 publications

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“…The other two subjects also presented with developmental delay associated with hypotonia and mild dystonic features. All reported subjects had congenital cataracts, and none had hearing loss [ 53 ].…”

Section: Mitochondrial Iron–sulfur Biosynthesis (Isc)mentioning

confidence: 99%

Clinical and genetic aspects of defects in the mitochondrial iron–sulfur cluster synthesis pathway

Vanlander

Coster

2018

J Biol Inorg Chem

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Iron–sulfur clusters are evolutionarily conserved biological structures which play an important role as cofactor for multiple enzymes in eukaryotic cells. The biosynthesis pathways of the iron–sulfur clusters are located in the mitochondria and in the cytosol. The mitochondrial iron–sulfur cluster biosynthesis pathway (ISC) can be divided into at least twenty enzymatic steps. Since the description of frataxin deficiency as the cause of Friedreich’s ataxia, multiple other deficiencies in ISC biosynthesis pathway have been reported. In this paper, an overview is given of the clinical, biochemical and genetic aspects reported in humans affected by a defect in iron–sulfur cluster biosynthesis.

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Section: Mitochondrial Iron–sulfur Biosynthesis (Isc)mentioning

confidence: 99%

Clinical and genetic aspects of defects in the mitochondrial iron–sulfur cluster synthesis pathway

Vanlander

Coster

2018

J Biol Inorg Chem

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“…This article is protected by copyright. All rights reserved (Table 1) [136][137][138][139]. Additional variable features of MPMCD include hearing loss, respiratory chain deficiency and hypotonia [136][137][138][139].…”

Section: Accepted Articlementioning

confidence: 99%

“…All rights reserved (Table 1) [136][137][138][139]. Additional variable features of MPMCD include hearing loss, respiratory chain deficiency and hypotonia [136][137][138][139]. The molecular mechanism of a number of these mutants has yet to be characterised, however characterisation of the R194H mutation revealed a COX deficiency, with reduced immunostaining of COX17, Tim13 and COX6B1 in patient fibroblasts [137].…”

Section: Accepted Articlementioning

confidence: 99%

Mitochondrial protein import dysfunction: mitochondrial disease, neurodegenerative disease and cancer

2021

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The majority of proteins localised to mitochondria are encoded by the nuclear genome, with approximately 1500 proteins imported into mammalian mitochondria. Dysfunction in this fundamental cellular process is linked to a variety of pathologies including neuropathies, cardiovascular disorders, myopathies, neurodegenerative diseases and cancer, demonstrating the importance of mitochondrial protein import machinery for cellular function. Correct import of proteins into mitochondria requires the co‐ordinated activity of multimeric protein translocation and sorting machineries located in both the outer and inner mitochondrial membranes, directing the imported proteins to the destined mitochondrial compartment. This dynamic process maintains cellular homeostasis, and its dysregulation significantly affects cellular signalling pathways and metabolism. This review summarises current knowledge of the mammalian mitochondrial import machinery and the pathological consequences of mutation of its components. In addition, we will discuss the role of mitochondrial import in cancer, and our current understanding of the role of mitochondrial import in neurodegenerative diseases including Alzheimer's disease, Huntington's disease and Parkinson's disease.

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“…There are eight patients in four families reported with mutations in the GFER gene [77,80,81] , to date. The age range of the patients was 3 to 21 years with one deceased at 21 years of age.…”

Section: Gfer Deficiency (Omim #613076)mentioning

confidence: 99%

“…The predominant features were neuromuscular including hypotonia and psychomotor retardation of variable severity, muscle hypotrophy, progressive muscle weakness requiring ventilatory support, and, additionally, cataracts and lactic acidosis. Other clinical features included movement disorder, dysautonomia, cachexia and orthopedic problems [81] , hearing loss [77] , and adrenal insufficiency [80] . MRI of the brain showed normal findings (4/6), cerebellar and moderate cortical atrophy (1/6), and thin corpus callosum (1/6).…”

Section: Gfer Deficiency (Omim #613076)mentioning

confidence: 99%

Riboflavin metabolism: role in mitochondrial function

Balasubramaniam¹,

Yaplito‐Lee²

2020

jtgg

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Riboflavin, known as vitamin B2, a water-soluble vitamin, is an essential nutrient in vertebrates, hence adequate dietary intake is imperative. Riboflavin plays a role in a variety of metabolic pathways, serving primarily as an integral component of its crucial biologically active forms, the flavocoenzymes flavin adenine dinucleotide and flavin mononucleotide. These flavocoenzymes ensure the functionality of numerous flavoproteins including dehydrogenases, oxidases, monooxygenases, and reductases, which play pivotal roles in mitochondrial electron transport chain, β-oxidation of fatty acids, redox homeostasis, citric acid cycle, branched-chain amino acid catabolism, chromatin remodeling, DNA repair, protein folding, and apoptosis. Unsurprisingly, impairment of flavin homeostasis in humans has been linked to various diseases including neuromuscular and neurological disorders, abnormal fetal development, and cardiovascular diseases. This review presents an overview of riboflavin metabolism, its role in mitochondrial function, primary and secondary flavocoenzyme defects associated with mitochondrial dysfunction, and the role of riboflavin supplementation in these conditions.

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Further delineation of a rare recessive encephalomyopathy linked to mutations in GFER thanks to data sharing of whole exome sequencing data

Abstract: This report highlights the clinical utility of whole exome sequencing and reverse phenotyping for the diagnosis of ultra-rare diseases and underlines the importance of a broad data sharing for accurate clinical delineation of previously unrecognized entities.

Cited by 21 publications

References 35 publications

Clinical and genetic aspects of defects in the mitochondrial iron–sulfur cluster synthesis pathway

Clinical and genetic aspects of defects in the mitochondrial iron–sulfur cluster synthesis pathway

Mitochondrial protein import dysfunction: mitochondrial disease, neurodegenerative disease and cancer

Riboflavin metabolism: role in mitochondrial function

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