Missense SLC25A38 variations play an important role in autosomal recessive inherited sideroblastic anemia
Autor/a
Kannengiesser, Caroline
Sanchez, Mayka
Sweeney, Marion
Hetet, Gilles
Kerr, Briedgeen
Moran, Erica
Fuster Soler, Jose L.
Maloum, Karim
Matthes, Thomas
Oudot, Caroline
Lascaux, Axelle
Pondarré, Corinne
Sevilla Navarro, Julian
Vidyatilake, Sudharma
Beaumont, Carole
Grandchamp, Bernard
May, Alison
Fecha de publicación
2011ISSN
0390-6078
Resumen
Congenital sideroblastic anemias are rare disorders with several genetic causes; they are characterized by erythroblast mitochondrial iron overload, differ greatly in severity and some occur within a syndrome. The most common cause of non-syndromic, microcytic sideroblastic anemia is a defect in the X-linked 5-aminolevulinate synthase 2 gene but this is not always present. Recently, variations in the gene for the mitochondrial carrier SLC25A38 were reported to cause a non-syndromic, severe type of autosomal-recessive sideroblastic anemia. Further evaluation of the importance of this gene was required to estimate the proportion of patients affected and to gain further insight into the range and types of variations involved. In three European diagnostic laboratories sequence analysis of was performed on DNA from patients affected by congenital sideroblastic anemia of a non-syndromic nature not caused by variations in the 5-aminolevulinate synthase 2 gene. Eleven patients whose ancestral origins spread across several continents were homozygous or compound heterozygous for ten different variations causing premature termination of translation (p.Arg117X, p.Tyr109LeufsX43), predicted splicing alteration (c.625G>C; p.Asp209His) or missense substitution (p.Gln56Lys, p.Arg134Cys, p.Ile147Asn, p.Arg187Gln, p.Pro190Arg, p.Gly228Val, p.Arg278Gly). Only three of these variations have been described previously (p.Arg117X, p.Tyr109LeufsX43 and p.Asp209His). All new variants reported here are missense and affect conserved amino acids. Structure modeling suggests that these variants may influence different aspects of transport as described for mutations in other mitochondrial carrier disorders. Mutations in the gene cause severe, non-syndromic, microcytic/hypochromic sideroblastic anemia in many populations. Missense mutations are shown to be of importance as are mutations that affect protein production. Further investigation of these mutations should shed light on structure-function relationships in this protein.
Tipo de documento
Artículo
Versión del documento
Versión publicada
Lengua
English
Materias (CDU)
61 - Medicina
Palabras clave
Anèmia sideroblàstica congènita
SLC25A38
Mutacions sense sentit
Anemia sideroblástica congénita
SLC25A38
Mutaciones sin sentido
Congenital sideroblastic anemia
SLC25A38
Missense mutations
Páginas
6
Publicado por
Ferrata Storti Foundation
Colección
96; 6
Publicado en
Haematologica
Citación
Kannengiesser, Caroline; Sanchez, Mayka; Sweeney, Marion [et al.]. Missense SLC25A38 variations play an important role in autosomal recessive inherited sideroblastic anemia. Haematologica, 2011, 96(6), p. 808-813. Disponible en: <https://haematologica.org/article/view/5986>. Fecha de acceso: 22 ene. 2024. DOI: 10.3324/haematol.2010.039164
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Derechos
©2011 Ferrata Storti Foundation. This is an open-access paper.