Identification of novel L2HGDH gene mutations and update of the pathological spectrum

Vilarinho, Laura; Tafulo, Sandra; Sibilio, Michelina; Kok, Fernando; Fontana, Federica; Diogo, Luísa; Venâncio, Margarida; Ferreira, Mariana; Nogueira, Célia; Valongo, Carla; Parenti, Giancarlo; Amorim, António; Azevedo, Luı́sa

doi:10.1038/jhg.2009.110

Cited by 6 publications

(9 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The diagnosis of L2HGA comprises of biochemical, radiological and genetic testing. The MRI abnormalities seen in the subcortical cerebral white matter, putamen, caudate nucleus, globus pallidus, and dentate nucleus are unique to L2HGA, and are used as baseline investigation [ 6 , 10 – 16 ]. The disease-causing gene is L-2-hydroxyglutarate dehydrogenase ( L2HGDH -NM_024884.2) which is located on chromosome 14q22.1 [MIM 609584] and comprises of 10 coding exons spanning 75 kb.…”

Section: Introductionmentioning

confidence: 99%

“…L2HGDH is a mitochondrial enzyme which catalyses oxidation of L-2-hydroxyglutarate (L2HG) to α2-ketoglutarate (α2KG); a metabolic product bound to mitochondrial membrane [ 15 , 17 ]. Several mutations L2HGDH have been reported worldwide in affected individuals belonging to various ethnic groups [ 6 , 8 , 13 – 16 , 18 , 19 ] ( http://grenada.lumc.nl/LOVD2/vumc/status.php ) [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Identification of novel L2HGDH mutation in a large consanguineous Pakistani family- a case report

et al. 2018

View full text Add to dashboard Cite

BackgroundL-2-hydroxyglutaric aciduria (L2HGA) is a progressive neurometabolic disease of brain caused by mutations of in L-2-hydroxyglutarate dehydrogenase (L2HGDH) gene. Cardinal clinical features include cerebellar ataxia, epilepsy, neurodevelopmental delay, intellectual disability, and other clinical neurological deficits.Case presentationWe describe an index case of the family presented with generalised tonic-clonic seizure, developmental delay, intellectual disability, and ataxia. Initially, the differential diagnosis was difficult to be established and a SNP genome wide scan identified the candidate region on chromosome 14q22.1. DNA sequencing showed a novel homozygous mutation in the candidate gene L2HGDH (NM_024884.2: c.178G > A; p.Gly60Arg). The mutation p.Gly60Arg lies in the highly conserved FAD/NAD(P)-binding domain of this mitochondrial enzyme, predicted to disturb enzymatic function.ConclusionsThe combination of homozygosity mapping and DNA sequencing identified a novel mutation in Pakistani family with variable clinical features. This is second report of a mutation in L2HGDH gene from Pakistan and the largest family with L2HGA reported to date.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of novel L2HGDH mutation in a large consanguineous Pakistani family- a case report

et al. 2018

View full text Add to dashboard Cite

show abstract

“… 7 , 10 Haplotyping showed that the Portuguese and Italian patients shared the mutation-carrying chromosome with identical SNP haplotypes, thus pointing to a common origin of the mutation in these 2 populations. 10 The Italian and Portuguese patients carried the c.159C allele (c.159T/C SNP, which is located 10 nucleotide upstream of the pathogenic c.169G>A mutation. 9 The finding of the homozygous c.159T allele associated with the c.169G>A mutation in Arab patients points to an independent origin of the c.169G>A mutation in Arab population.…”

Section: Discussionmentioning

confidence: 93%

“… 6 – 8 , 10 In a recent study, the c.169G>A mutation (p.Gly57Arg) that was originally found in a compound heterozygous state in a Portuguese female was discovered in a homozygous state in an Italian male patient. 7 , 10 Haplotyping showed that the Portuguese and Italian patients shared the mutation-carrying chromosome with identical SNP haplotypes, thus pointing to a common origin of the mutation in these 2 populations. 10 The Italian and Portuguese patients carried the c.159C allele (c.159T/C SNP, which is located 10 nucleotide upstream of the pathogenic c.169G>A mutation.…”

Section: Discussionmentioning

confidence: 99%

“…This metabolic disorder is caused by mutations in the L-2-hydroxyglutarate dehydrogenase (L2HGDH) gene at chromosome 14q22.1, which encodes for the L-2-hydroxyglutarate dehydrogenase. 6 – 10 The L2HGDH gene is expressed in multiple tissues with the strongest expression in the brain. 6 The L-2-hydroxyglutarate dehydrogenase catalyzes the oxidation of L-2-hydroxyglutaric acid to 2-ketoglutaric acid.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Clinical, neuroimaging, and genetic features of L-2-hydroxyglutaric aciduria in Arab kindreds

Faiyaz-Ul-Haque

AlSayed

Faqeih

et al. 2014

Annals of Saudi Medicine

View full text Add to dashboard Cite

BACKGROUND AND OBJECTIVESL-2-hydroxyglutaric aciduria is a neurometabolic disorder with autosomal recessive mode of inheritance in which patients exhibit elevated L-2-hydroxyglutaric acid in body fluids, central nervous system manifestations, and increased risk of brain tumor formation. Mutations in L2HGDH gene have been described in L-2-hydroxyglutaric aciduria patients of different ethnicities. The present study was conducted to perform a detailed clinical, imaging and genetic analysis.DESIGN AND SETTINGSA cross-sectional clinical genetic study of 16 L-2-hydroxyglutaric aciduria patients from 4 Arab consanguineous families examined at the metabolic clinic of the hospital.PATIENTS AND METHODSGenomic DNA was isolated from the blood of 12 patients and 10 unaffected family members, and the L2HGDH gene was sequenced. DNA sequences were compared to the L2HGDH reference sequence from GenBank.RESULTSAll patients exhibit characteristic clinical, biochemical, and imaging features of L-2-hydroxyglutaric aciduria, and 4 patients exhibited increased incidence of brain tumors. The sequencing of the L2HGDH gene revealed the c.1015delA, c.1319C>A, and c.169G>A mutations in these patients. These mutations encode for the p.Arg339AspfsX351, p.Ser440Tyr, and p.Gly57Arg changes in the L2HGDH protein, respectively. The c.169G>A mutation, which was shown to have a common origin in Italian and Portuguese patients, was also discovered in Arab patients. Finding of the homozygous c.159T SNP associated with the c.169G>A mutation in Arab patients points to an independent origin of this mutation in Arab population.CONCLUSIONThe detailed description of clinical manifestations and L2HGDH mutation in this study is useful for diagnosis of L-2-hydroxyglutaric aciduria in Arab patients. While reoccurrence of an L2HGDH mutation in L-2-hydroxyglutaric aciduria patients of different ethnicity is extremely rare, the c.169G mutation has an independent origin in Arab patients. It is likely that this mutation may also be present in patients of other ethnicities.

show abstract

A novel compound heterozygous mutation of the L2HGDH gene in a Chinese boy with L-2-hydroxyglutaric aciduria: case report and literature review

et al. 2018

View full text Add to dashboard Cite

show abstract

Identification of novel L2HGDH gene mutations and update of the pathological spectrum

Cited by 6 publications

References 15 publications

Identification of novel L2HGDH mutation in a large consanguineous Pakistani family- a case report

Identification of novel L2HGDH mutation in a large consanguineous Pakistani family- a case report

Clinical, neuroimaging, and genetic features of L-2-hydroxyglutaric aciduria in Arab kindreds

A novel compound heterozygous mutation of the L2HGDH gene in a Chinese boy with L-2-hydroxyglutaric aciduria: case report and literature review

Contact Info

Product

Resources

About