Source:http://linkedlifedata.com/resource/pubmed/id/16134148
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2005-9-5
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| pubmed:databankReference | |
| pubmed:abstractText |
We studied 21 patients, from 18 families, with L-2-hydroxyglutaric aciduria (L-2-HGA), a rare neurometabolic disorder with a homogeneous presentation: progressive neurodegeneration with extrapyramidal and cerebellar signs, seizures, and subcortical leukoencephalopathy. Increased levels of L-2-hydroxyglutaric acid in body fluids proved the diagnosis of L-2-HGA in all 21 patients. We analyzed the L-2-HGA gene (L2HGDH), recently found to be mutated in consanguineous families with L-2-HGA, and identified seven novel mutations in 15 families. Three mutations appeared to be particularly prevalent in this Portuguese panel: a frameshift mutation (c.529delC) was detected in 12 out of 30 mutant alleles (40%), a nonsense mutation (c.208C>T; p.Arg70X) in 7/30 alleles (23%), and a missense mutation (c.293A>G; p.His98Arg) in four out of 30 mutant alleles (13%), suggesting that common origin may exist. Furthermore, two novel missense (c.169G>A; p.Gly57Arg, c.1301A>C; p.His434Pro) and two splice error (c.257-2A>G, c.907-2A>G) mutations were found. All the mutations presumably lead to loss-of-function with no relationship between clinical signs, progression of the disease, levels of L-2-HGA and site of the mutation. In the three remaining families, no pathogenic mutations in the L-2-HGA were found, which suggests either alterations in regulatory regions of the gene or of its intervening sequences, compound heterozygosity for large genomic deletion and, or further genetic heterogeneity.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
1098-1004
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| pubmed:author |
pubmed-author:AlegriaPP,
pubmed-author:AmorimAA,
pubmed-author:AzevedoLL,
pubmed-author:BarboyNN,
pubmed-author:Cabral FernandesHH,
pubmed-author:CabralPP,
pubmed-author:CardosoM LML,
pubmed-author:CarrilhoII,
pubmed-author:ChorãoRR,
pubmed-author:DiogoLL,
pubmed-author:FinezaII,
pubmed-author:GasparPP,
pubmed-author:JakobsCC,
pubmed-author:KonKK,
pubmed-author:MartiniSS,
pubmed-author:SalomonsG SGS,
pubmed-author:SantorelliF MFM,
pubmed-author:SantosMM,
pubmed-author:TeixeiraJJ,
pubmed-author:VerhoevenN MNM,
pubmed-author:VilarinhoLL
|
| pubmed:copyrightInfo |
(c) 2005 Wiley-Liss, Inc.
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| pubmed:issnType |
Electronic
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| pubmed:volume |
26
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
395-6
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:16134148-Adolescent,
pubmed-meshheading:16134148-Adult,
pubmed-meshheading:16134148-Alcohol Oxidoreductases,
pubmed-meshheading:16134148-Amino Acid Sequence,
pubmed-meshheading:16134148-Animals,
pubmed-meshheading:16134148-Child,
pubmed-meshheading:16134148-Child, Preschool,
pubmed-meshheading:16134148-Cohort Studies,
pubmed-meshheading:16134148-Consanguinity,
pubmed-meshheading:16134148-Family Health,
pubmed-meshheading:16134148-Female,
pubmed-meshheading:16134148-Glutarates,
pubmed-meshheading:16134148-Humans,
pubmed-meshheading:16134148-Male,
pubmed-meshheading:16134148-Middle Aged,
pubmed-meshheading:16134148-Molecular Sequence Data,
pubmed-meshheading:16134148-Mutation,
pubmed-meshheading:16134148-Portugal,
pubmed-meshheading:16134148-Sequence Alignment,
pubmed-meshheading:16134148-Sequence Analysis, DNA
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| pubmed:year |
2005
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| pubmed:articleTitle |
Novel L2HGDH mutations in 21 patients with L-2-hydroxyglutaric aciduria of Portuguese origin.
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| pubmed:affiliation |
Clinical Biology Unit, Medical Genetics Institute, Porto, Portugal. laura.vilarinho@igm.min-saude.pt
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|