FAOD and oxidative stress

• July 21st, 2011

Mice models of VLCAD develop oxidative stress in the liver upon fasting, suggesting reactive oxygen species are important culprits in the hepatopathy of affected patients (Tucci et al, 2010, FEBS J 277:4699-708). Increased oxidative stress was also seen when over-expressing a mutant SCAD in cultured cells (Schmidt et al, 2010, Mol Genet Metab 100:155-62), while others noticed increased autophagy (Shirao et al, 2010, Hum Genet 127:619-28); the second possibly being a consequence of the first.

Posted by Philippe Campeau, MD

IDH1 mutation in gliomas

• April 7th, 2010

Certain gliomas have somatic mutation in cytosolic isocitrate dehydrogenase 1. Dang et al. have shown that these mutations confer the enzyme the new ability to transform alpha-ketoglutarate in 2-hydroxyglutarate. This metabolite might be oncogenic, although this is not proven yet.

Dang L, White DW, Gross S, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2009;462:739-744

Philippe Campeau

Succinate dehydrogenase and leukoencephalopathy

• July 27th, 2009

A gene encoding a protein essential for the assembly of succinate dehydrogenase has been implicated in an infantile leukoencephalopathy.

Nat Genet. 2009 May 24. [Epub ahead of print]

SDHAF1, encoding a LYR complex-II specific assembly factor, is mutated in SDH-defective infantile leukoencephalopathy.

Ghezzi D et al.

Click this link to see the most recent online abstracts of major genetics journals.

Philippe Campeau

Mitochondrial carrier and sideroblastic anemia

• July 27th, 2009

Nat Genet. 2009 Jun;41(6):651-3. Epub 2009 May 3.

Mutations in mitochondrial carrier family gene SLC25A38 cause nonsyndromic autosomal recessive congenital sideroblastic anemia.

Guernsey DL et al.

These investigators form Nova Scotia describe a new form of sideroblastic anemia caused by a mutation in a mitochondrial carrier. The gene was identified by positional cloning.

Click this link to see the most recent online abstracts of major genetics journals.

Philippe Campeau

New cause of CoQ10 deficiency

• July 27th, 2009

Am J Hum Genet. 2009 May;84(5):558-66. Epub 2009 Apr 16.

A nonsense mutation in COQ9 causes autosomal-recessive neonatal-onset primary coenzyme Q10 deficiency: a potentially treatable form of mitochondrial disease.

Duncan AJ et al.

This group from the UK describes a new form of coQ10 deficiency, a potentially treatable condition.

Click this link to see the most recent online abstracts of major genetics journals.

Philippe Campeau

New Krebs cycle defect

• October 6th, 2008

Nat Genet. 2008 Oct;40(10):1230-4. Epub 2008 Sep 21.

Insights from retinitis pigmentosa into the roles of isocitrate dehydrogenases in the Krebs cycle.

Hartong DT, Dange M, McGee TL, Berson EL, Dryja TP, Colman RF.

We still have things to learn about the Krebs cycle….
Indeed, by studying families with Retinitis Pigmentosa, Hartong and colleagues identified individuals with functional defects in NAD-specific isocitrate dehydrogenase.
What is surprinsing is that these individuals do not have a generalized mitochondrial syndrome with encephalopathy (seen in homozygotes with defects of other enzymes of the krebs cycle) but the only affected organ is the retina. It is believed that elsewhere in the body, NADP-specific isocitrate dehydrogenase catalyzes the oxidation of isocitrate to alpha-ketoglutarate.

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Click this link to see the most recent online abstracts of major genetics journals.

Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

Another gene involved in ubiquinone deficiency

• April 10th, 2008

Am J Hum Genet. 2008 Mar;82(3):623-30.

CABC1 gene mutations cause ubiquinone deficiency with cerebellar ataxia and
seizures.

Mollet J, Delahodde A, Serre V, Chretien D, Schlemmer D, Lombes A, Boddaert N,
Desguerre I, de Lonlay P, de Baulny HO, Munnich A, Rötig A.

Investigators rom Paris have studied patients with CoQ10 deficiency from three families (presenting mostly with myopathy and ataxia), and systematically sequenced genes in the ubiquinone biosynthesis pathway. Mutations were found in CABC1, and the mutations were proven to be pathogenic in a yeast model. The role of the protein encoded by this gene is not precisely known yet.

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Click this link to see the most recent online abstracts of major genetics journals.
Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

Reversion of white matter changes with treatment of HMG-CoA lyase deficiency.

• December 19th, 2007

Pediatr Neurol. 2007 Jul;37(1):47-50.

3-Hydroxy-3-methylglutaryl coenzyme a lyase deficiency with reversible white
matter changes after treatment.

Zafeiriou DI, Vargiami E, Mayapetek E, Augoustidou-Savvopoulou P, Mitchell GA.

Click this link to see the most recent online abstracts of major genetics journals.
Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

• August 25th, 2007

A group led by Orly Elpeleg has identified a gene associated with pontocerebellar hypoplasia, a heterogenous group of conditions.

Deleterious Mutation in the Mitochondrial ArginylTransfer RNA Synthetase Gene Is Associated with Pontocerebellar Hypoplasia
Simon Edvardson, Avraham Shaag, Olga Kolesnikova, John Moshe Gomori, Ivan Tarassov, Tom Einbinder, Ann Saada, and Orly Elpeleg
The American Journal of Human Genetics, volume 81 (2007),   
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Click this link to see the most recent online abstracts of major genetics journals.
Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator

A lethal defect of mitochondrial and peroxisomal fission

• June 24th, 2007

N Engl J Med. 2007 Apr 26;356(17):1707-9.

A lethal defect of mitochondrial and peroxisomal fission.

Waterham HR, Koster J, van Roermund CW, Mooyer PA, Wanders RJ, Leonard JV.

girl with microcephaly, abnormal brain development, optic atrophy and hypoplasia. Biochemical analyses revealed lactic acidosis and an increase in very-long-chain fatty acids.

Because the peroxisomes and mitochondria in fibroblasts from the patient were similar to those in cells overexpressing dominant negative mutant DLP1, they sequenced this gene in their patient and found mutations.

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Philippe Campeau, MD
Resident in Medical Genetics at McGill University
OMMBID Blog Administrator