Rescue of primary ubiquinone deficiency due to a novel COQ7 defect using 2,4-dihydroxybensoic acid.
J Med Genet
; 52(11): 779-83, 2015 Nov.
Article
em En
| MEDLINE
| ID: mdl-26084283
ABSTRACT
BACKGROUND:
Coenzyme Q is an essential mitochondrial electron carrier, redox cofactor and a potent antioxidant in the majority of cellular membranes. Coenzyme Q deficiency has been associated with a range of metabolic diseases, as well as with some drug treatments and ageing.METHODS:
We used whole exome sequencing (WES) to investigate patients with inherited metabolic diseases and applied a novel ultra-pressure liquid chromatography-mass spectrometry approach to measure coenzyme Q in patient samples.RESULTS:
We identified a homozygous missense mutation in the COQ7 gene in a patient with complex mitochondrial deficiency, resulting in severely reduced coenzyme Q levels We demonstrate that the coenzyme Q analogue 2,4-dihydroxybensoic acid (2,4DHB) was able to specifically bypass the COQ7 deficiency, increase cellular coenzyme Q levels and rescue the biochemical defect in patient fibroblasts.CONCLUSION:
We report the first patient with primary coenzyme Q deficiency due to a homozygous COQ7 mutation and a potentially beneficial treatment using 2,4DHB.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ataxia
/
Ubiquinona
/
Debilidade Muscular
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Mutação de Sentido Incorreto
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Doenças Mitocondriais
/
Hidroxibenzoatos
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Child
/
Child, preschool
/
Humans
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Male
/
Newborn
Idioma:
En
Revista:
J Med Genet
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Suécia