A recurring mutation in the respiratory complex 1 protein NDUFB11 is responsible for a novel form of X-linked sideroblastic anemia.
Blood
; 128(15): 1913-1917, 2016 10 13.
Article
em En
| MEDLINE
| ID: mdl-27488349
ABSTRACT
The congenital sideroblastic anemias (CSAs) are a heterogeneous group of inherited blood disorders characterized by pathological mitochondrial iron deposition in erythroid precursors. Each known cause has been attributed to a mutation in a protein associated with heme biosynthesis, iron-sulfur cluster biogenesis, mitochondrial translation, or a component of the mitochondrial respiratory chain. Here, we describe a recurring mutation, c.276_278del, p.F93del, in NDUFB11, a mitochondrial respiratory complex I-associated protein encoded on the X chromosome, in 5 males with a variably syndromic, normocytic CSA. The p.F93del mutation results in respiratory insufficiency and loss of complex I stability and activity in patient-derived fibroblasts. Targeted introduction of this allele into K562 erythroleukemia cells results in a proliferation defect with minimal effect on erythroid differentiation potential, suggesting the mechanism of anemia in this disorder.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sequência de Bases
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Deleção de Sequência
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Cromossomos Humanos X
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Doenças Genéticas Ligadas ao Cromossomo X
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Complexo I de Transporte de Elétrons
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Anemia Sideroblástica
Limite:
Adolescent
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Adult
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Aged
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Child
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Child, preschool
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Blood
Ano de publicação:
2016
Tipo de documento:
Article