An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype-phenotype study
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype-phenotype study. / 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.
I: Human Mutation, Bind 31, Nr. 4, 01.04.2010, s. 380-90.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - An overview of L-2-hydroxyglutarate dehydrogenase gene (L2HGDH) variants: a genotype-phenotype study
AU - Steenweg, Marjan E
AU - Jakobs, Cornelis
AU - Errami, Abdellatif
AU - van Dooren, Silvy J M
AU - Adeva Bartolomé, Maria T
AU - Aerssens, Peter
AU - Augoustides-Savvapoulou, Persephone
AU - Baric, Ivo
AU - Baumann, Matthias
AU - Bonafé, Luisa
AU - Chabrol, Brigitte
AU - Clarke, Joe T R
AU - Clayton, Peter
AU - Coker, Mahmut
AU - Cooper, Sarah
AU - Falik-Zaccai, Tzipora
AU - Gorman, Mark
AU - Hahn, Andreas
AU - Hasanoglu, Alev
AU - King, Mary D
AU - de Klerk, Hans B C
AU - Korman, Stanley H
AU - Lee, Céline
AU - Meldgaard Lund, Allan
AU - Mejaski-Bosnjak, Vlatka
AU - Pascual-Castroviejo, Ignacio
AU - Raadhyaksha, Aparna
AU - Rootwelt, Terje
AU - Roubertie, Agathe
AU - Ruiz-Falco, Maria L
AU - Scalais, Emmanuel
AU - Schimmel, Ulf
AU - Seijo-Martinez, Manuel
AU - Suri, Mohnish
AU - Sykut-Cegielska, Jolanta
AU - Trefz, Friedrich K
AU - Uziel, Graziella
AU - Valayannopoulos, Vassili
AU - Vianey-Saban, Christine
AU - Vlaho, Stefan
AU - Vodopiutz, Julia
AU - Wajner, Moacir
AU - Walter, John
AU - Walter-Derbort, Claudia
AU - Yapici, Zuhal
AU - Zafeiriou, Dimitrios I
AU - Spreeuwenberg, Marieke D
AU - Celli, Jacopo
AU - den Dunnen, Johan T
AU - van der Knaap, Marjo S
AU - Salomons, Gajja S
N1 - (c) 2010 Wiley-Liss, Inc.
PY - 2010/4/1
Y1 - 2010/4/1
N2 - 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.
AB - 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.
U2 - http://dx.doi.org/10.1002/humu.21197
DO - http://dx.doi.org/10.1002/humu.21197
M3 - Journal article
VL - 31
SP - 380
EP - 390
JO - Human Mutation
JF - Human Mutation
SN - 1059-7794
IS - 4
ER -
ID: 34150240