Repositório Científico do Instituto Nacional de Saúde >
Departamento de Genética Humana >
DGH - Artigos em revistas internacionais >

Please use this identifier to cite or link to this item: http://hdl.handle.net/10400.18/179

Título: Molecular characterization of five patients with homocystinuria due to severe methylenetetrahydrofolate reductase deficiency
Autor: Urreizti, R.
Moya-García, A. A.
Pino-Ángeles, A.
Cozar, M.
Langkilde, A.
Fanhoe, U.
Esteves, C.
Arribas, J.
Vilaseca, M.A.
Pérez-Dueñas, B.
Pineda, M.
González, V.
Artuch, R.
Baldellou, A.
Vilarinho, L.
Fowler, B.
Ribes, A.
Sánchez-Jiménez, F.
Grinberg, D.
Balcells, S.
Palavras-chave: Homocystinuria
MTHFR
Deficiency
Structure modelling
Mutations
NMD
Mefolinate
Treatment
Doenças Genéticas
Issue Date: Nov-2010
Editora: Wiley
Citação: Clin Genet. 2010 Nov;78(5):441-8
Resumo: Methylenetetrahydrofolate reductase (MTHFR) plays a major role in folate metabolism. Disturbed function of the enzyme results in hyperhomocysteinemia and causes severe vascular and neurological disorders and developmental delay. Five patients suspected of having non-classical homocystinuria due to MTHFR deficiency were examined with respect to their symptoms, MTHFR enzyme activity and genotypes of the MTHFR gene. All patients presented symptoms of severe central nervous system disease. Two patients died, at the ages of 15 months and 14 years. One patient is currently 32 years old, and is being treated with betaine and folinic acid. The other two patients, with an early diagnosis and a severe course of the disease, are currently improving under treatment. MTHFR enzyme activity in the fibroblasts of four of the patients was practically undetectable. We found four novel mutations, three of which were missense changes c.664G>T (p.V218L), c.1316T>C (p.F435S) and c.1733T>G (p.V574G), and the fourth was the 1-bp deletion c.1780delC (p.L590CfsX72). We also found the previously reported nonsense mutation c.1420G>T (p.E470X). All the patients were homozygous. Molecular modelling of the double mutant allele (p.V218L; p.A222V) revealed that affinity for FAD was not affected in this mutant. For the p.E470X mutation, the evidence pointed to nonsense-mediated mRNA decay. In general, genotype–phenotype analysis predicts milder outcomes for patients with missense changes than for those in which mutations led to severe alterations of the MTHFR protein.
Arbitragem científica: yes
URI: http://hdl.handle.net/10400.18/179
ISSN: 0009-9163
Versão do Editor: http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0009-9163&date=2010&volume=78&issue=5&spage=441
Appears in Collections:DGH - Artigos em revistas internacionais

Files in This Item:

File Description SizeFormat
Molecular characterization of five.pdf337,33 kBAdobe PDFView/Open
Restrict Access. You can request a copy!
Statistics
FacebookTwitterDeliciousLinkedInDiggGoogle BookmarksMySpaceOrkut
Formato BibTex mendeley Endnote Logotipo do DeGóis 

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

 

  © 2010 www.insa.pt - Todos os direitos reservados | Feedback Ministério da Saúde
Promotores do RCAAP   Financiadores do RCAAP

Fundação para a Ciência e a Tecnologia Universidade do Minho   Governo Português Ministério da Educação e Ciência PO Sociedade do Conhecimento (POSC) Portal oficial da União Europeia