The severity of phenotype linked to SUCLG1 mutations could be correlated with residual amount of SUCLG1 protein

Rouzier, Cécile; Guédard-Méreuze, Sandie Le; Fragaki, Konstantina; Serre, Valérie; Miro, Julie; Tuffery‐Giraud, Sylvie; Chaussenot, Annabelle; Bannwarth, Sylvie; Caruba, C.; Østergaard, Elsebet; Pellissier, J.-F.; Richelme, Christian; Espil, Caroline; Chabrol, B.; Paquis‐Flucklinger, Véronique

doi:10.1136/jmg.2009.073445

Cited by 49 publications

(27 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…10,11 The search for mtDNA heteroplasmic mutations was done by using Surveyor method. 12 Microsatellite DNA markers flanking 17 genes involved in the CoQ 10 biosynthesis pathway were analyzed.…”

Section: Molecular Analysismentioning

confidence: 99%

Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency

et al. 2012

View full text Add to dashboard Cite

We report two children, born from consanguineous parents, who presented with early-onset refractory epilepsy associated with psychomotor delay, failure to thrive, blindness and deafness. Polarographic and spectrophotometric analyses in fibroblasts and liver revealed a respiratory chain (RC) dysfunction. Surprisingly, we identified a homozygous nonsense mutation in the GM3 synthase gene by using exome sequencing. GM3 synthase catalyzes the formation of GM3 ganglioside from lactosylceramide, which is the first step in the synthesis of complex ganglioside species. Mass spectrometry analysis revealed that the complete absence of GM3 ganglioside and its biosynthetic derivatives was associated with an upregulation of the alternative globoside pathway in fibroblasts. The accumulation of Gb3 and Gb4 globosides likely has a role in RC dysfunction and in the decrease of mitochondrial membrane potential leading to apoptosis, which we observed in fibroblasts. We show for the first time that GM3 synthase deficiency, responsible for early-onset epilepsy syndrome, leads to a secondary RC dysfunction. Our study highlights the role of secondary mitochondrial disorders that can interfere with the diagnosis and the evolution of other metabolic diseases.

show abstract

Section: Molecular Analysismentioning

confidence: 99%

Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency

et al. 2012

View full text Add to dashboard Cite

show abstract

“…SUCLA2 [21] (OMIM *603921) defects present with muscle hypotonia, severe psychomotor retardation, impaired hearing, general seizures followed by knee and hip contractures, finger dystonia and ptosis [21][22][23]. SUCLG1 [24] (OMIM *611224) defects are associated with a more severe phenotype, including a combination of muscle and liver dysfunction and dysmorphic features [24], but similar phenotypes to that of patients with SUCLA2 mutations have been described [25,26]. A characteristic metabolic profile (mild increase of methylmalonic acid and C4-DC carnitine in urine) and Leigh syndrome with basal ganglia MRI lesions were previously identified as the hallmarks of SUCLA2 and SUCLG1 mutations [27].…”

Section: Introductionmentioning

confidence: 84%

Mitochondrial DNA depletion syndrome: New descriptions and the use of citrate synthase as a helpful tool to better characterise the patients

Navarro-Sastre

Tort

García-Villoria

et al. 2012

Molecular Genetics and Metabolism

View full text Add to dashboard Cite

“…Almost all the patients have increased urinary excretion of methylmalonic acid that should be considered as a useful marker although recently two cases without methylmalonic aciduria have been reported [ 57 , 58 ]. SUCLG1 is rarer and presents with a similar, but usually worse phenotype and more severe mtDNA depletion in the muscle [ 59 ].…”

Section: Encephalomyopathic Forms: Mds5 Mds8a and Mds9mentioning

confidence: 93%

Mitochondrial Genes and Neurodegenerative Disease

Viscomi

Ardissone²,

Zeviani

2016

Mitochondrial Dysfunction in Neurodegenerative Disorders

View full text Add to dashboard Cite

Mitochondrial dysfunction is increasingly recognised as a cause of neurodegeneration in both primary mitochondrial diseases and common neurodegenerative diseases, including Parkinson's, Alzheimer's and Huntington's diseases and amyotrophic lateral sclerosis (ALS).In this chapter, we will focus on the molecular basis of mitochondrial dysfunction and the mechanisms bridging it to neurodegeneration. In the fi rst part, we will summarise some basic concepts of mitochondrial biology. We will then cover paediatric diseases, including different types of encephalopathies, Leigh disease, leukoencephalopathies and a variety of syndromes with peculiar features. Finally, we will cover diseases in adults, including MNGIE disease, Friedreich ataxia and the disorders associated with alterations in mitochondrial dynamics and quality control. These include axonal Charcot-Marie-Tooth neuropathy, hereditary spastic paraplegia, and autosomal dominant optic atrophy, as well as the inherited and idiopathic forms of common neurodegenerative diseases.

show abstract

The severity of phenotype linked to SUCLG1 mutations could be correlated with residual amount of SUCLG1 protein

Cited by 49 publications

References 25 publications

Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency

Refractory epilepsy and mitochondrial dysfunction due to GM3 synthase deficiency

Mitochondrial DNA depletion syndrome: New descriptions and the use of citrate synthase as a helpful tool to better characterise the patients

Mitochondrial Genes and Neurodegenerative Disease

Contact Info

Product

Resources

About