Lethal hepatopathy and leukodystrophy caused by a novel mutation in MPV17 gene: description of an alternative MPV17 spliced form.
Mol Genet Metab
; 94(2): 234-9, 2008 Jun.
Article
em En
| MEDLINE
| ID: mdl-18329934
ABSTRACT
It has recently been reported that mutations in MPV17 gene may be causative of mtDNA depletion syndrome (MDS). Patients with this alteration presented with severe liver failure, hypoglycemia, growth retardation and neurological symptoms during the first year of life. We report on the clinical, biochemical and molecular findings of a patient presenting with lethal hepatopathy, polyneuropathy, neurological regression and leukodystrophy associated with mutations in MPV17. Mitochondrial respiratory chain activities were low in liver and within reference values in muscle. However, levels of mtDNA were markedly reduced both in muscle and liver. A novel homozygous mutation in MPV17, c.70+5G>A (IVS1+5G>A), was identified. This intronic change causes the full-length cDNA loss, probably due to loss of strength of the splice donor site of exon 1. Western blot analysis, performed in liver homogenates, further corroborates these results as the amount of patient's protein was highly reduced, or almost absent, compared with that of controls. We also identified an additional alternative spliced form in controls and in the patient, due to exon 2 skipping, that has not previously been reported.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Processamento Alternativo
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Doenças Mitocondriais
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Proteínas Mitocondriais
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Leucodistrofia de Células Globoides
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Hepatopatias
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Proteínas de Membrana
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Mutação
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Limite:
Humans
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Male
/
Newborn
Idioma:
En
Revista:
Mol Genet Metab
Assunto da revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
/
METABOLISMO
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Espanha