* 609584

L-2-HYDROXYGLUTARATE DEHYDROGENASE; L2HGDH


Alternative titles; symbols

DURANIN
CHROMOSOME 14 OPEN READING FRAME 160; C14ORF160


HGNC Approved Gene Symbol: L2HGDH

Cytogenetic location: 14q21.3     Genomic coordinates (GRCh38): 14:50,242,434-50,312,229 (from NCBI)


Gene-Phenotype Relationships
Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
14q21.3 L-2-hydroxyglutaric aciduria 236792 AR 3

TEXT

Cloning and Expression

Ota et al. (2004) determined the complete sequence of cDNA corresponding to the C14ORF160 gene, which was derived from a full-length human cDNA library.

Topcu et al. (2004) determined that the C14ORF160 gene (L2HGDH) encodes a 463-amino acid protein containing a domain that defines a family of FAD-dependent oxidoreductases located in mitochondria or peroxisomes. They showed that mouse and rat orthologs exhibit 86% homology in coding sequence and more than 69% homology in amino acid sequence. Topcu et al. (2004) also identified a splice variant of 441 amino acids identical to the long form of the protein through the first 399 residues.


Gene Function

By RT-PCR, Topcu et al. (2004) demonstrated that L2HGDH is expressed in multiple tissues, with strongest expression in brain, followed by testis and muscle. Expression was weaker in lymphocytes, fibroblasts, keratinocytes, and placenta, and weakest in bladder, small intestine, liver, and bone marrow.

In assays of alpha-ketoglutarate with L-glutamate dehydrogenase, Rzem et al. (2004) demonstrated that L-2-hydroxyglutarate was oxidized to the corresponding 2-keto acid, and concluded that L-2-hydroxyglutarate is normally metabolized to alpha-ketoglutarate in mammalian tissues.


Gene Structure

Topcu et al. (2004) determined that the L2HGDH gene is composed of 10 exons. Mouse and rat orthologs have similar organization.


Mapping

Topcu et al. (2004) identified the L2HGDH gene within a 1.07-Mb critical interval on chromosome 14q22.1 for L-2-hydroxyglutaric aciduria (236792), defined by homozygosity mapping.


Molecular Genetics

Topcu et al. (2004) identified mutations in the L2HGDH gene in 21 patients with L-2-hydroxyglutaric aciduria from 15 families, 14 of them consanguineous. Nine homozygous mutations included 3 missense mutations, 2 nonsense mutations, 2 splice site mutations, and 2 deletions.

In 3 consanguineous families with L-2-hydroxyglutaric aciduria, of Belgian, Tunisian, and Lebanese origin, respectively, Rzem et al. (2004) identified homozygosity for 3 different mutations in the L2HGDH gene that cosegregated with the disease in each family. Taken together with their biochemical findings (see GENE FUNCTION), Rzem et al. (2004) concluded that the pathologic findings in this metabolic disorder are due to a toxic effect of L-2-hydroxyglutarate on the central nervous system.

In 6 patients from 5 families with L-2-hydroxyglutaric aciduria, Vilarinho et al. (2010) identified homozygous or compound heterozygous mutations in the L2HGDH gene (see, e.g., 609584.0006). The patients were of Portuguese, Italian, and Brazilian descent. The authors stated that 35 mutations had been reported in the L2HGDH gene.

Najmabadi et al. (2011) performed homozygosity mapping followed by exon enrichment and next-generation sequencing in 136 consanguineous families (over 90% Iranian and less than 10% Turkish or Arab) segregating syndromic or nonsyndromic forms of autosomal recessive intellectual disability. In a family (8600276) in which 4 of 7 children had L-2-hydroxyglutaric aciduria and profound intellectual disability and were unable to walk, Najmabadi et al. (2011) identified homozygosity for a nonsense mutation in the L2HGDH gene (609584.0007) in all of those affected. The parents were distantly related.


Nomenclature

Topcu et al. (2004) proposed that the product of the L2HGDH gene be named 'duranin' in honor of Marinus Duran, who first described L-2-hydroxyglutaric aciduria (Duran et al., 1980).


Animal Model

Canine Model

Penderis et al. (2007) described a spontaneous canine model of L-2-hydroxyglutaric aciduria in outbred Staffordshire bull terriers. Twenty-one affected dogs all showed increased urinary L-2-HG, and 12 dogs in whom MRI imaging was done showed symmetric regions of hyperintensity similar to that seen in humans with the disorder. Homozygosity mapping and direct sequencing identified a homozygous mutation in exon 10 of the canine L2hgdh gene in all affected animals. Pedigree analysis indicated a founder effect.

Mouse Model

Ma et al. (2017) observed age-dependent accumulation of L-2-hydroxyglutarate in cerebrum and alterations in a subset of histone methylations in the central nervous system of L2hgdh -/- mice. Mutant mice exhibited subcortical white matter abnormalities, recapitulating clinical features of patients with L-2-hydroxyglutaric aciduria. L2hgdh mice also showed dys/demyelination, extensive gliosis, expanded oligodendrocyte progenitor cell numbers, and microglia-mediated neuroinflammation. Additionally, L2hgdh -/- mice had impaired adult hippocampal neurogenesis, as well as age-dependent neurodegeneration.

Feline Model

Christen et al. (2021) described a 7-month-old cat with L-2-hydroxyglutaric aciduria. The cat developed paroxysmal seizure-like episodes and hallucination-type episodes at 3 months of age. Between seizure episodes, the neurologic exam was normal except for absence of a bilateral menace response. A brain MRI demonstrated multifocal, symmetric hyperintensities in the diencephalon, mesencephalon, and metencephalon primarily affecting gray matter. Urine organic acid testing identified increased L-2-hydroxyglutaric acid. Whole-genome sequencing followed by Sanger sequencing confirmation showed homozygosity for a c.1301A-G transition (XM_023255678.1) in the L2HGDH gene, resulting in a his434-to-arg substitution. The mutation was not identified in 48 control cat genomes. The affected cat was treated with keppra and phenobarbital, which successfully managed the seizures.


ALLELIC VARIANTS ( 7 Selected Examples):

.0001 L-2-HYDROXYGLUTARIC ACIDURIA

L2HGDH, PRO302LEU
  
RCV000001674...

In members of 2 consanguineous Turkish families with L-2-hydroxyglutaric aciduria (L2HGA; 236792), Topcu et al. (2004) reported homozygosity for a 905C-T transition in exon 7 of the L2HGDH gene, which was predicted to result in a substitution of leucine for proline at residue 302 (P302L).


.0002 L-2-HYDROXYGLUTARIC ACIDURIA

L2HGDH, 1-BP DEL, 1115T
  
RCV000001675

In 2 consanguineous Turkish families with L-2-hydroxyglutaric aciduria (L2HGA; 236792), Topcu et al. (2004) described homozygosity for deletion of thymidine at nucleotide position 1115 in exon 9 of the L2HGDH gene, which was predicted to result in a premature stop codon.


.0003 L-2-HYDROXYGLUTARIC ACIDURIA

L2HGDH, IVS7DS, G-T, +1
  
RCV000001676

In 2 members of a consanguineous Turkish family with L-2-hydroxyglutaric aciduria (L2HGA; 236792), Topcu et al. (2004) reported homozygosity for a 906G-T transversion in intron 7 of the L2HGDH gene, which was predicted to result in aberrant splicing of exon 7.


.0004 L-2-HYDROXYGLUTARIC ACIDURIA

L2HGDH, GLY55ASP
  
RCV000001677...

In members of 3 consanguineous Turkish families with L-2-hydroxyglutaric aciduria (L2HGA; 236792), Topcu et al. (2004) described homozygosity for a 164G-A transition in exon 2 of the L2HGDH gene, which was predicted to result in a substitution of aspartic acid for glycine at residue 55 (G55D).


.0005 L-2-HYDROXYGLUTARIC ACIDURIA

L2HGDH, EX1-9DEL
   RCV000001678

In a child of a consanguineous Turkish family with L-2-hydroxyglutaric aciduria (L2HGA; 236792), Topcu et al. (2004) reported homozygosity for a large genomic deletion in the L2HGDH gene that eliminated exons 1 through 9.


.0006 L-2-HYDROXYGLUTARIC ACIDURIA

L2HGDH, HIS98ARG
  
RCV000001679...

In 2 unrelated Portuguese patients with L-2-hydroxyglutaric aciduria (L2HGA; 236792), Vilarinho et al. (2010) identified a homozygous 293A-G transition in the L2HGDH gene, resulting in a his98-to-arg (H98R) substitution in a conserved residue.


.0007 L-2-HYDROXYGLUTARIC ACIDURIA

L2HGDH, ARG335TER
  
RCV000023778

Najmabadi et al. (2011) identified a family (8600276) in which 4 of 7 children of distantly related parents had L-2-hydroxyglutaric aciduria (L2HGA; 236792) and profound intellectual disability. Affected individuals were homozygous for a G-to-A transition at genomic coordinate chr14:49,804,282 (NCBI36), resulting in an arg335-to-ter (R335X) substitution. Both parents were carriers.


REFERENCES

  1. Christen, M., Janzen, N., Fraser, A., Sewell, A. C., Jagannathan, V., Guevar, J., Leeb, T., Sanchez-Masian, D. L2HGDH missense variant in a cat with L-2-hydroxyglutaric aciduria. Genes 12: 682, 2021. [PubMed: 34062805, images, related citations] [Full Text]

  2. Duran, M., Kamerling, J. P., Bakker, H. D., van Gennip, A. H., Wadman, S. K. L-2-hydroxyglutaric aciduria: an inborn error of metabolism? J. Inherit. Metab. Dis. 3: 109-112, 1980. [PubMed: 6787330, related citations] [Full Text]

  3. Ma, S., Sun, R., Jiang, B., Gao, J., Deng, W., Liu, P., He, R., Cui, J., Ji, M., Yi, W., Yang, P., Wu, X., Xiong, Y., Qiu, Z., Ye, D., Guan, K.-L. L2hgdh deficiency accumulates L-2-hydroxyglutarate with progressive leukoencephalopathy and neurodegeneration. Molec. Cell. Biol. 37: e00492-16, 2017. Note: Electronic Article. [PubMed: 28137912, images, related citations] [Full Text]

  4. Najmabadi, H., Hu, H., Garshasbi, M., Zemojtel, T., Abedini, S. S., Chen, W., Hosseini, M., Behjati, F., Haas, S., Jamali, P., Zecha, A., Mohseni, M., and 33 others. Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Nature 478: 57-63, 2011. [PubMed: 21937992, related citations] [Full Text]

  5. Ota, T., Suzuki, Y., Nishikawa, T., Otsuki, T., Sugiyama, T., Irie, R., Wakamatsu, A., Hayashi, K., Sato, H., Nagai, K., Kimura, K., Makita, H. and 145 others. Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature Genet 36: 40-45, 2004. [PubMed: 14702039, related citations] [Full Text]

  6. Penderis, J., Calvin, J., Abramson, C., Jakobs, C., Pettitt, L., Binns, M. M., Verhoeven, N. M., O'Driscoll, E., Platt, S. R., Mellersh, C. S. L-2-hydroxyglutaric aciduria: characterisation of the molecular defect in a spontaneous canine model. (Letter) J. Med. Genet. 44: 334-340, 2007. [PubMed: 17475916, images, related citations] [Full Text]

  7. Rzem, R., Veiga-da-Cunha, M., Noel, G., Goffette, S., Nassogne, M.-C., Tabarki, B., Scholler, C., Marquardt, T., Vikkula, M., Van Schaftingen, E. A gene encoding a putative FAD-dependent L-2-hydroxyglutarate dehydrogenase is mutated in L-2-hydroxyglutaric aciduria. Proc. Nat. Acad. Sci. 101: 16849-16854, 2004. [PubMed: 15548604, images, related citations] [Full Text]

  8. Topcu, M., Jobard, F., Halliez, S., Coskun, T., Yalcinkayal, C., Gerceker, F. O., Wanders, R. J. A., Prud'homme, J.-F., Lathrop, M., Ozguc, M., Fischer, J. L-2-hydroxyglutaric aciduria: identification of a mutant gene C14orf160, localized on chromosome 14q22.1. Hum. Molec. Genet. 13: 2803-2811, 2004. [PubMed: 15385440, related citations] [Full Text]

  9. Vilarinho, L., Tafulo, S., Sibilio, M., Kok, F., Fontana, F., Diogo, L., Venancio, M., Ferreira, M., Nogueira, C., Valongo, C., Parenti, G., Amorim, A., Azevedo, L. Identification of novel L2HGDH gene mutations and update of the pathologic spectrum. J. Hum. Genet. 55: 55-58, 2010. [PubMed: 19911013, related citations] [Full Text]


Hilary J. Vernon - updated : 12/22/2021
Paul J. Converse - updated : 11/07/2017
Ada Hamosh - updated : 1/6/2012
Cassandra L. Kniffin - updated : 6/14/2010
Cassandra L. Kniffin - updated : 6/22/2007
Marla J. F. O'Neill - updated : 9/28/2005
Creation Date:
George E. Tiller : 9/16/2005
carol : 01/04/2022
carol : 12/22/2021
carol : 08/02/2021
carol : 07/26/2018
mgross : 11/07/2017
mgross : 11/07/2017
carol : 07/24/2015
alopez : 4/8/2015
joanna : 3/11/2015
carol : 1/9/2012
terry : 1/6/2012
wwang : 6/18/2010
ckniffin : 6/14/2010
wwang : 7/2/2007
ckniffin : 6/22/2007
wwang : 10/7/2005
terry : 9/28/2005
alopez : 9/16/2005

* 609584

L-2-HYDROXYGLUTARATE DEHYDROGENASE; L2HGDH


Alternative titles; symbols

DURANIN
CHROMOSOME 14 OPEN READING FRAME 160; C14ORF160


HGNC Approved Gene Symbol: L2HGDH

SNOMEDCT: 237961001;  


Cytogenetic location: 14q21.3     Genomic coordinates (GRCh38): 14:50,242,434-50,312,229 (from NCBI)


Gene-Phenotype Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
14q21.3 L-2-hydroxyglutaric aciduria 236792 Autosomal recessive 3

TEXT

Cloning and Expression

Ota et al. (2004) determined the complete sequence of cDNA corresponding to the C14ORF160 gene, which was derived from a full-length human cDNA library.

Topcu et al. (2004) determined that the C14ORF160 gene (L2HGDH) encodes a 463-amino acid protein containing a domain that defines a family of FAD-dependent oxidoreductases located in mitochondria or peroxisomes. They showed that mouse and rat orthologs exhibit 86% homology in coding sequence and more than 69% homology in amino acid sequence. Topcu et al. (2004) also identified a splice variant of 441 amino acids identical to the long form of the protein through the first 399 residues.


Gene Function

By RT-PCR, Topcu et al. (2004) demonstrated that L2HGDH is expressed in multiple tissues, with strongest expression in brain, followed by testis and muscle. Expression was weaker in lymphocytes, fibroblasts, keratinocytes, and placenta, and weakest in bladder, small intestine, liver, and bone marrow.

In assays of alpha-ketoglutarate with L-glutamate dehydrogenase, Rzem et al. (2004) demonstrated that L-2-hydroxyglutarate was oxidized to the corresponding 2-keto acid, and concluded that L-2-hydroxyglutarate is normally metabolized to alpha-ketoglutarate in mammalian tissues.


Gene Structure

Topcu et al. (2004) determined that the L2HGDH gene is composed of 10 exons. Mouse and rat orthologs have similar organization.


Mapping

Topcu et al. (2004) identified the L2HGDH gene within a 1.07-Mb critical interval on chromosome 14q22.1 for L-2-hydroxyglutaric aciduria (236792), defined by homozygosity mapping.


Molecular Genetics

Topcu et al. (2004) identified mutations in the L2HGDH gene in 21 patients with L-2-hydroxyglutaric aciduria from 15 families, 14 of them consanguineous. Nine homozygous mutations included 3 missense mutations, 2 nonsense mutations, 2 splice site mutations, and 2 deletions.

In 3 consanguineous families with L-2-hydroxyglutaric aciduria, of Belgian, Tunisian, and Lebanese origin, respectively, Rzem et al. (2004) identified homozygosity for 3 different mutations in the L2HGDH gene that cosegregated with the disease in each family. Taken together with their biochemical findings (see GENE FUNCTION), Rzem et al. (2004) concluded that the pathologic findings in this metabolic disorder are due to a toxic effect of L-2-hydroxyglutarate on the central nervous system.

In 6 patients from 5 families with L-2-hydroxyglutaric aciduria, Vilarinho et al. (2010) identified homozygous or compound heterozygous mutations in the L2HGDH gene (see, e.g., 609584.0006). The patients were of Portuguese, Italian, and Brazilian descent. The authors stated that 35 mutations had been reported in the L2HGDH gene.

Najmabadi et al. (2011) performed homozygosity mapping followed by exon enrichment and next-generation sequencing in 136 consanguineous families (over 90% Iranian and less than 10% Turkish or Arab) segregating syndromic or nonsyndromic forms of autosomal recessive intellectual disability. In a family (8600276) in which 4 of 7 children had L-2-hydroxyglutaric aciduria and profound intellectual disability and were unable to walk, Najmabadi et al. (2011) identified homozygosity for a nonsense mutation in the L2HGDH gene (609584.0007) in all of those affected. The parents were distantly related.


Nomenclature

Topcu et al. (2004) proposed that the product of the L2HGDH gene be named 'duranin' in honor of Marinus Duran, who first described L-2-hydroxyglutaric aciduria (Duran et al., 1980).


Animal Model

Canine Model

Penderis et al. (2007) described a spontaneous canine model of L-2-hydroxyglutaric aciduria in outbred Staffordshire bull terriers. Twenty-one affected dogs all showed increased urinary L-2-HG, and 12 dogs in whom MRI imaging was done showed symmetric regions of hyperintensity similar to that seen in humans with the disorder. Homozygosity mapping and direct sequencing identified a homozygous mutation in exon 10 of the canine L2hgdh gene in all affected animals. Pedigree analysis indicated a founder effect.

Mouse Model

Ma et al. (2017) observed age-dependent accumulation of L-2-hydroxyglutarate in cerebrum and alterations in a subset of histone methylations in the central nervous system of L2hgdh -/- mice. Mutant mice exhibited subcortical white matter abnormalities, recapitulating clinical features of patients with L-2-hydroxyglutaric aciduria. L2hgdh mice also showed dys/demyelination, extensive gliosis, expanded oligodendrocyte progenitor cell numbers, and microglia-mediated neuroinflammation. Additionally, L2hgdh -/- mice had impaired adult hippocampal neurogenesis, as well as age-dependent neurodegeneration.

Feline Model

Christen et al. (2021) described a 7-month-old cat with L-2-hydroxyglutaric aciduria. The cat developed paroxysmal seizure-like episodes and hallucination-type episodes at 3 months of age. Between seizure episodes, the neurologic exam was normal except for absence of a bilateral menace response. A brain MRI demonstrated multifocal, symmetric hyperintensities in the diencephalon, mesencephalon, and metencephalon primarily affecting gray matter. Urine organic acid testing identified increased L-2-hydroxyglutaric acid. Whole-genome sequencing followed by Sanger sequencing confirmation showed homozygosity for a c.1301A-G transition (XM_023255678.1) in the L2HGDH gene, resulting in a his434-to-arg substitution. The mutation was not identified in 48 control cat genomes. The affected cat was treated with keppra and phenobarbital, which successfully managed the seizures.


ALLELIC VARIANTS 7 Selected Examples):

.0001   L-2-HYDROXYGLUTARIC ACIDURIA

L2HGDH, PRO302LEU
SNP: rs118204020, gnomAD: rs118204020, ClinVar: RCV000001674, RCV002274874

In members of 2 consanguineous Turkish families with L-2-hydroxyglutaric aciduria (L2HGA; 236792), Topcu et al. (2004) reported homozygosity for a 905C-T transition in exon 7 of the L2HGDH gene, which was predicted to result in a substitution of leucine for proline at residue 302 (P302L).


.0002   L-2-HYDROXYGLUTARIC ACIDURIA

L2HGDH, 1-BP DEL, 1115T
SNP: rs786200869, ClinVar: RCV000001675

In 2 consanguineous Turkish families with L-2-hydroxyglutaric aciduria (L2HGA; 236792), Topcu et al. (2004) described homozygosity for deletion of thymidine at nucleotide position 1115 in exon 9 of the L2HGDH gene, which was predicted to result in a premature stop codon.


.0003   L-2-HYDROXYGLUTARIC ACIDURIA

L2HGDH, IVS7DS, G-T, +1
SNP: rs786200870, ClinVar: RCV000001676

In 2 members of a consanguineous Turkish family with L-2-hydroxyglutaric aciduria (L2HGA; 236792), Topcu et al. (2004) reported homozygosity for a 906G-T transversion in intron 7 of the L2HGDH gene, which was predicted to result in aberrant splicing of exon 7.


.0004   L-2-HYDROXYGLUTARIC ACIDURIA

L2HGDH, GLY55ASP
SNP: rs118204021, ClinVar: RCV000001677, RCV003398413

In members of 3 consanguineous Turkish families with L-2-hydroxyglutaric aciduria (L2HGA; 236792), Topcu et al. (2004) described homozygosity for a 164G-A transition in exon 2 of the L2HGDH gene, which was predicted to result in a substitution of aspartic acid for glycine at residue 55 (G55D).


.0005   L-2-HYDROXYGLUTARIC ACIDURIA

L2HGDH, EX1-9DEL
ClinVar: RCV000001678

In a child of a consanguineous Turkish family with L-2-hydroxyglutaric aciduria (L2HGA; 236792), Topcu et al. (2004) reported homozygosity for a large genomic deletion in the L2HGDH gene that eliminated exons 1 through 9.


.0006   L-2-HYDROXYGLUTARIC ACIDURIA

L2HGDH, HIS98ARG
SNP: rs267607206, ClinVar: RCV000001679, RCV000522298

In 2 unrelated Portuguese patients with L-2-hydroxyglutaric aciduria (L2HGA; 236792), Vilarinho et al. (2010) identified a homozygous 293A-G transition in the L2HGDH gene, resulting in a his98-to-arg (H98R) substitution in a conserved residue.


.0007   L-2-HYDROXYGLUTARIC ACIDURIA

L2HGDH, ARG335TER
SNP: rs387907013, gnomAD: rs387907013, ClinVar: RCV000023778

Najmabadi et al. (2011) identified a family (8600276) in which 4 of 7 children of distantly related parents had L-2-hydroxyglutaric aciduria (L2HGA; 236792) and profound intellectual disability. Affected individuals were homozygous for a G-to-A transition at genomic coordinate chr14:49,804,282 (NCBI36), resulting in an arg335-to-ter (R335X) substitution. Both parents were carriers.


REFERENCES

  1. Christen, M., Janzen, N., Fraser, A., Sewell, A. C., Jagannathan, V., Guevar, J., Leeb, T., Sanchez-Masian, D. L2HGDH missense variant in a cat with L-2-hydroxyglutaric aciduria. Genes 12: 682, 2021. [PubMed: 34062805] [Full Text: https://doi.org/10.3390/genes12050682]

  2. Duran, M., Kamerling, J. P., Bakker, H. D., van Gennip, A. H., Wadman, S. K. L-2-hydroxyglutaric aciduria: an inborn error of metabolism? J. Inherit. Metab. Dis. 3: 109-112, 1980. [PubMed: 6787330] [Full Text: https://doi.org/10.1007/BF02312543]

  3. Ma, S., Sun, R., Jiang, B., Gao, J., Deng, W., Liu, P., He, R., Cui, J., Ji, M., Yi, W., Yang, P., Wu, X., Xiong, Y., Qiu, Z., Ye, D., Guan, K.-L. L2hgdh deficiency accumulates L-2-hydroxyglutarate with progressive leukoencephalopathy and neurodegeneration. Molec. Cell. Biol. 37: e00492-16, 2017. Note: Electronic Article. [PubMed: 28137912] [Full Text: https://doi.org/10.1128/MCB.00492-16]

  4. Najmabadi, H., Hu, H., Garshasbi, M., Zemojtel, T., Abedini, S. S., Chen, W., Hosseini, M., Behjati, F., Haas, S., Jamali, P., Zecha, A., Mohseni, M., and 33 others. Deep sequencing reveals 50 novel genes for recessive cognitive disorders. Nature 478: 57-63, 2011. [PubMed: 21937992] [Full Text: https://doi.org/10.1038/nature10423]

  5. Ota, T., Suzuki, Y., Nishikawa, T., Otsuki, T., Sugiyama, T., Irie, R., Wakamatsu, A., Hayashi, K., Sato, H., Nagai, K., Kimura, K., Makita, H. and 145 others. Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature Genet 36: 40-45, 2004. [PubMed: 14702039] [Full Text: https://doi.org/10.1038/ng1285]

  6. Penderis, J., Calvin, J., Abramson, C., Jakobs, C., Pettitt, L., Binns, M. M., Verhoeven, N. M., O'Driscoll, E., Platt, S. R., Mellersh, C. S. L-2-hydroxyglutaric aciduria: characterisation of the molecular defect in a spontaneous canine model. (Letter) J. Med. Genet. 44: 334-340, 2007. [PubMed: 17475916] [Full Text: https://doi.org/10.1136/jmg.2006.042507]

  7. Rzem, R., Veiga-da-Cunha, M., Noel, G., Goffette, S., Nassogne, M.-C., Tabarki, B., Scholler, C., Marquardt, T., Vikkula, M., Van Schaftingen, E. A gene encoding a putative FAD-dependent L-2-hydroxyglutarate dehydrogenase is mutated in L-2-hydroxyglutaric aciduria. Proc. Nat. Acad. Sci. 101: 16849-16854, 2004. [PubMed: 15548604] [Full Text: https://doi.org/10.1073/pnas.0404840101]

  8. Topcu, M., Jobard, F., Halliez, S., Coskun, T., Yalcinkayal, C., Gerceker, F. O., Wanders, R. J. A., Prud'homme, J.-F., Lathrop, M., Ozguc, M., Fischer, J. L-2-hydroxyglutaric aciduria: identification of a mutant gene C14orf160, localized on chromosome 14q22.1. Hum. Molec. Genet. 13: 2803-2811, 2004. [PubMed: 15385440] [Full Text: https://doi.org/10.1093/hmg/ddh300]

  9. Vilarinho, L., Tafulo, S., Sibilio, M., Kok, F., Fontana, F., Diogo, L., Venancio, M., Ferreira, M., Nogueira, C., Valongo, C., Parenti, G., Amorim, A., Azevedo, L. Identification of novel L2HGDH gene mutations and update of the pathologic spectrum. J. Hum. Genet. 55: 55-58, 2010. [PubMed: 19911013] [Full Text: https://doi.org/10.1038/jhg.2009.110]


Contributors:
Hilary J. Vernon - updated : 12/22/2021
Paul J. Converse - updated : 11/07/2017
Ada Hamosh - updated : 1/6/2012
Cassandra L. Kniffin - updated : 6/14/2010
Cassandra L. Kniffin - updated : 6/22/2007
Marla J. F. O'Neill - updated : 9/28/2005

Creation Date:
George E. Tiller : 9/16/2005

Edit History:
carol : 01/04/2022
carol : 12/22/2021
carol : 08/02/2021
carol : 07/26/2018
mgross : 11/07/2017
mgross : 11/07/2017
carol : 07/24/2015
alopez : 4/8/2015
joanna : 3/11/2015
carol : 1/9/2012
terry : 1/6/2012
wwang : 6/18/2010
ckniffin : 6/14/2010
wwang : 7/2/2007
ckniffin : 6/22/2007
wwang : 10/7/2005
terry : 9/28/2005
alopez : 9/16/2005