RGD Reference Report - Founder effect confirmation of c.241A>G mutation in the L2HGDH gene and characterization of oxidative stress parameters in six Tunisian families with L-2-hydroxyglutaric aciduria. - Rat Genome Database

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Founder effect confirmation of c.241A>G mutation in the L2HGDH gene and characterization of oxidative stress parameters in six Tunisian families with L-2-hydroxyglutaric aciduria.

Authors: Jellouli, Nadege Kammoun  Hadj Salem, Ikhlass  Ellouz, Emna  Kamoun, Zeineb  kamoun, Fatma  tlili, Abdelaziz  Kaabachi, Naziha  Triki, Chanez  Fakhfakh, Faiza  Tunisian Network on Mental Retardation study,  
Citation: Jellouli NK, etal., J Hum Genet. 2014 Apr;59(4):216-22. doi: 10.1038/jhg.2014.4. Epub 2014 Feb 27.
RGD ID: 13506824
Pubmed: PMID:24573090   (View Abstract at PubMed)
DOI: DOI:10.1038/jhg.2014.4   (Journal Full-text)

L-2-hydroxyglutaric aciduria (L2HGA) is an autosomal recessive neurometabolic disorder characterized essentially by the presence of elevated levels of L-2-hydroxyglutaric acid (LGA) in plasma, cerebrospinal fluid and urine. L2HGA is caused by a deficiency in the L2-Hydroxyglutaric dehydrogenase (L2HGDH) enzyme involved in the oxidation of LGA to the alpha 2-ketoglutarate. LGA has been proposed as an endo- and exogenous cytotoxic organic acid that induces free radical formation and generation of reactive oxygen species (ROS). In this report, we analyzed 14 L2HGA patients belonging to six unrelated consanguineous families the south of Tunisia. The patients were diagnosed with L2HGA disease confirmed on the presence of high level of LGA in urine. We analyzed the L2HGDH gene in all probands and identified the same c.241A>G homozygous mutation, which was previously reported in Tunisia. We also used intragenic single nucleotide length polymorphisms (SNPs) and two extragenic microsatellites flanking the L2HGDH gene to confirm the founder effect of c.241A>G mutation in the 14 studied cases. In addition, we carried out the measurement of the oxidative stress parameters in the plasma of L2HGA patients which revealed a significant increase in the malondialdehyde levels (MDA), a biomarker of lipid peroxydation, and the reduced glutathione (GSH). A diminution of the antioxidant enzyme activities including superoxide dismutase (SOD), glutathione peroxidase (GPx), was also observed.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cerebellar ataxia  IAGP 13506824DNA:mutation:cds:c.241A4G(p.K81E)(human)RGD 
cerebellar ataxia  ISOL2HGDH (Homo sapiens)13506824; 13506824DNA:mutation:cds:c.241A4G(p.K81E)(human)RGD 
hereditary spastic paraplegia  IAGP 13506824DNA:mutation:cds:c.241A4G(p.K81E)(human)RGD 
hereditary spastic paraplegia  ISOL2HGDH (Homo sapiens)13506824; 13506824DNA:mutation:cds:c.241A4G(p.K81E)(human)RGD 
L-2-hydroxyglutaric aciduria  IAGP 13506824DNA:mutation:cds:c.241A4G(p.K81E)(human)RGD 
L-2-hydroxyglutaric aciduria  ISOL2HGDH (Homo sapiens)13506824; 13506824DNA:mutation:cds:c.241A4G(p.K81E)(human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
L2hgdh  (L-2-hydroxyglutarate dehydrogenase)

Genes (Mus musculus)
L2hgdh  (L-2-hydroxyglutarate dehydrogenase)

Genes (Homo sapiens)
L2HGDH  (L-2-hydroxyglutarate dehydrogenase)


Additional Information