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

Authors :
Steenweg, Marjan E
Jakobs, Cornelis
Errami, Abdellatif
van Dooren, Silvy J M
Adeva Bartolomé, Maria T
Aerssens, Peter
Augoustides-Savvapoulou, Persephone
Baric, Ivo
Baumann, Matthias
Bonafé, Luisa
Chabrol, Brigitte
Clarke, Joe T R
Clayton, Peter
Coker, Mahmut
Cooper, Sarah
Falik-Zaccai, Tzipora
Gorman, Mark
Hahn, Andreas
Hasanoglu, Alev
King, Mary D
de Klerk, Hans B C
Korman, Stanley H
Lee, Céline
Meldgaard Lund, Allan
Mejaski-Bosnjak, Vlatka
Pascual-Castroviejo, Ignacio
Raadhyaksha, Aparna
Rootwelt, Terje
Roubertie, Agathe
Ruiz-Falco, Maria L
Scalais, Emmanuel
Schimmel, Ulf
Seijo-Martinez, Manuel
Suri, Mohnish
Sykut-Cegielska, Jolanta
Trefz, Friedrich K
Uziel, Graziella
Valayannopoulos, Vassili
Vianey-Saban, Christine
Vlaho, Stefan
Vodopiutz, Julia
Wajner, Moacir
Walter, John
Walter-Derbort, Claudia
Yapici, Zuhal
Zafeiriou, Dimitrios I
Spreeuwenberg, Marieke D
Celli, Jacopo
den Dunnen, Johan T
van der Knaap, Marjo S
Salomons, Gajja S
Steenweg, Marjan E
Jakobs, Cornelis
Errami, Abdellatif
van Dooren, Silvy J M
Adeva Bartolomé, Maria T
Aerssens, Peter
Augoustides-Savvapoulou, Persephone
Baric, Ivo
Baumann, Matthias
Bonafé, Luisa
Chabrol, Brigitte
Clarke, Joe T R
Clayton, Peter
Coker, Mahmut
Cooper, Sarah
Falik-Zaccai, Tzipora
Gorman, Mark
Hahn, Andreas
Hasanoglu, Alev
King, Mary D
de Klerk, Hans B C
Korman, Stanley H
Lee, Céline
Meldgaard Lund, Allan
Mejaski-Bosnjak, Vlatka
Pascual-Castroviejo, Ignacio
Raadhyaksha, Aparna
Rootwelt, Terje
Roubertie, Agathe
Ruiz-Falco, Maria L
Scalais, Emmanuel
Schimmel, Ulf
Seijo-Martinez, Manuel
Suri, Mohnish
Sykut-Cegielska, Jolanta
Trefz, Friedrich K
Uziel, Graziella
Valayannopoulos, Vassili
Vianey-Saban, Christine
Vlaho, Stefan
Vodopiutz, Julia
Wajner, Moacir
Walter, John
Walter-Derbort, Claudia
Yapici, Zuhal
Zafeiriou, Dimitrios I
Spreeuwenberg, Marieke D
Celli, Jacopo
den Dunnen, Johan T
van der Knaap, Marjo S
Salomons, Gajja S
Source :
Steenweg , M E , Jakobs , C , Errami , A , van Dooren , S J M , Adeva Bartolomé , M T , Aerssens , P , Augoustides-Savvapoulou , P , Baric , I , Baumann , M , Bonafé , L , Chabrol , B , Clarke , J T R , Clayton , P , Coker , M , Cooper , S , Falik-Zaccai , T , Gorman , M , Hahn , A , Hasanoglu , A , King , M D , de Klerk , H B C , 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 2010 , ' An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype-phenotype study ' , Human Mutation , vol. 31 , no. 4 , pp. 380-90 .
Publication Year :
2010

Abstract

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.

Details

Database :
OAIster
Journal :
Steenweg , M E , Jakobs , C , Errami , A , van Dooren , S J M , Adeva Bartolomé , M T , Aerssens , P , Augoustides-Savvapoulou , P , Baric , I , Baumann , M , Bonafé , L , Chabrol , B , Clarke , J T R , Clayton , P , Coker , M , Cooper , S , Falik-Zaccai , T , Gorman , M , Hahn , A , Hasanoglu , A , King , M D , de Klerk , H B C , 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 2010 , ' An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype-phenotype study ' , Human Mutation , vol. 31 , no. 4 , pp. 380-90 .
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1322183426
Document Type :
Electronic Resource