An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype-phenotype study.

Détails

ID Serval
serval:BIB_E8A2F6936DC0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype-phenotype study.
Périodique
Human Mutation
Auteur⸱e⸱s
Steenweg M.E., Jakobs C., Errami A., van Dooren S.J., Adeva Bartolomé M.T., Aerssens P., Augoustides-Savvapoulou P., Baric I., Baumann M., Bonafé L., Chabrol B., Clarke J.T., Clayton P., Coker M., Cooper S., Falik-Zaccai T., Gorman M., Hahn A., Hasanoglu A., King M.D., de Klerk H.B., Korman S.H., Lee C., Meldgaard Lund A., Mejaski-Bosnjak V., Pascual-Castroviejo I., Raadhyaksha A., Rootwelt T., Roubertie A., Ruiz-Falco M.L., Scalais E., Schimmel U., Seijo-Martinez M., Suri M., Sykut-Cegielska J., Trefz F.K., Uziel G., Valayannopoulos V., Vianey-Saban C., Vlaho S., Vodopiutz J., Wajner M., Walter J., Walter-Derbort C., Yapici Z., Zafeiriou D.I., Spreeuwenberg M.D., Celli J., den Dunnen J.T., van der Knaap M.S., Salomons G.S.
ISSN
1098-1004[electronic], 1059-7794[linking]
Statut éditorial
Publié
Date de publication
01/2010
Peer-reviewed
Oui
Volume
31
Numéro
4
Pages
380-390
Langue
anglais
Résumé
L-2-Hydroxyglutaric aciduria (L2HGA) is a rare, neurometabolic disorder with an autosomal recessive mode of inheritance. Affected individuals only have neurological manifestations, including psychomotor retardation, cerebellar ataxia, and more variably macrocephaly, or epilepsy. The diagnosis of L2HGA can be made based on magnetic resonance imaging (MRI), biochemical analysis, and mutational analysis of L2HGDH. About 200 patients with elevated concentrations of 2-hydroxyglutarate (2HG) in the urine were referred for chiral determination of 2HG and L2HGDH mutational analysis. All patients with increased L2HG (n=106; 83 families) were included. Clinical information on 61 patients was obtained via questionnaires. In 82 families the mutations were detected by direct sequence analysis and/or multiplex ligation dependent probe amplification (MLPA), including one case where MLPA was essential to detect the second allele. In another case RT-PCR followed by deep intronic sequencing was needed to detect the mutation. Thirty-five novel mutations as well as 35 reported mutations and 14 nondisease-related variants are reviewed and included in a novel Leiden Open source Variation Database (LOVD) for L2HGDH variants (http://www.LOVD.nl/L2HGDH). Every user can access the database and submit variants/patients. Furthermore, we report on the phenotype, including neurological manifestations and urinary levels of L2HG, and we evaluate the phenotype-genotype relationship.
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/02/2010 10:56
Dernière modification de la notice
20/08/2019 16:11
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