RESUMEN
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.
Asunto(s)
Anemia Sideroblástica/genética , Enfermedades Genéticas Ligadas al Cromosoma X/genética , Proteínas HSP70 de Choque Térmico/genética , Proteínas Mitocondriales/genética , Adulto , Anciano , Secuencia de Bases , Análisis Mutacional de ADN , Femenino , Genotipo , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Mutación , Análisis de Secuencia por Matrices de Oligonucleótidos , Linaje , Polimorfismo de Nucleótido Simple , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adulto JovenRESUMEN
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.