RESUMO
The congenital sideroblastic anemias (CSAs) are relatively uncommon diseases characterized by defects in mitochondrial heme synthesis, iron-sulfur (Fe-S) cluster biogenesis, or protein synthesis. Here we demonstrate that mutations in HSPA9, a mitochondrial HSP70 homolog located in the chromosome 5q deletion syndrome 5q33 critical deletion interval and involved in mitochondrial Fe-S biogenesis, result in CSA inherited as an autosomal recessive trait. In a fraction of patients with just 1 severe loss-of-function allele, expression of the clinical phenotype is associated with a common coding single nucleotide polymorphism in trans that correlates with reduced messenger RNA expression and results in a pseudodominant pattern of inheritance.
Assuntos
Anemia Sideroblástica/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Proteínas de Choque Térmico HSP70/genética , Proteínas Mitocondriais/genética , Adulto , Idoso , Sequência de Bases , Análise Mutacional de DNA , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação , Análise de Sequência com Séries de Oligonucleotídeos , Linhagem , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto JovemRESUMO
Recently various new gene defects have been identified which explain some previously unknown causes of inherited microcytic anaemias. These defects are located in genes that encode for the cellular iron importing protein Divalent Metal Transporter 1 (DMT1), the iron exporting protein ferroportin, the mitochondrial enzyme glutaredoxin-5 and the hepatocyte membrane protein matriptase-2.
