Publications

Authors:

Lira Zidanes, Acaynne; Marchi, Giacomo; Busti, Fabiana; Marchetto, Alessandro; Fermo, Elisa; Giorgetti, Alejandro; Vianello, Alice; Castagna, Annalisa; Olivieri, Oliviero; Bianchi, Paola; Girelli, Domenico

Title:

A Novel ALAS2 Missense Mutation in Two Brothers With Iron Overload and Associated Alterations in Serum Hepcidin/Erythroferrone Levels

Year:

2020

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Referee:

No

Name of journal:

FRONTIERS IN PHYSIOLOGY

ISSN of journal:

1664-042X

N° Volume:

11

Page numbers:

1-8

Keyword:

ALAS2 gene; ERFE; XLSA; hepcidin; in silico modeling; iron-loading anemias; next-generation sequencing

Short description of contents:

Iron loading anemias are characterized by ineffective erythropoiesis and iron overload. The prototype is non-transfusion dependent ß-thalassemia (NTDT), with other entities including congenital sideroblastic anemias, congenital dyserythropoietic anemias, some hemolytic anemias, and myelodysplastic syndromes. Differential diagnosis of iron loading anemias may be challenging due to heterogeneous genotype and phenotype. Notwithstanding the recent advances in linking ineffective erythropoiesis to iron overload, many pathophysiologic aspects are still unclear. Moreover, measurement of hepcidin and erythroferrone (ERFE), two key molecules in iron homeostasis and erythropoiesis, is scarcely used in clinical practice and of uncertain utility. Here, we describe a comprehensive diagnostic approach, including next-generation sequencing (NGS), in silico modeling, and measurement of hepcidin and erythroferrone (ERFE), in two brothers eventually diagnosed as X-linked sideroblastic anemia (XLSA). A novel pathogenic ALAS2 missense mutation (c.1382T>A, p.Leu461His) is described. Hyperferritinemia with high hepcidin-25 levels (but decreased hepcidin:ferritin ratio) and mild-to-moderate iron overload were detected in both patients. ERFE levels were markedly elevated in both patients, especially in the proband, who had a more expressed phenotype. Our study illustrates how new technologies, such as NGS, in silico modeling, and measurement of serum hepcidin-25 and ERFE, may help in diagnosing and studying iron loading anemias. Further studies on the hepcidin-25/ERFE axis in additional patients with XLSA and other iron loading anemias may help in establishing its usefulness in differential diagnosis, and it may also aid our understanding of the pathophysiology of these genetically and phenotypically heterogeneous entities.

Product ID:

119047

Handle IRIS:

11562/1034976

Last Modified:

December 2, 2022

Bibliographic citation:

Lira Zidanes, Acaynne; Marchi, Giacomo; Busti, Fabiana; Marchetto, Alessandro; Fermo, Elisa; Giorgetti, Alejandro; Vianello, Alice; Castagna, Annalisa; Olivieri, Oliviero; Bianchi, Paola; Girelli, Domenico, A Novel ALAS2 Missense Mutation in Two Brothers With Iron Overload and Associated Alterations in Serum Hepcidin/Erythroferrone Levels «FRONTIERS IN PHYSIOLOGY» , vol. 11 , 2020 , pp. 1-8

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