Identification of new causative genes has provided improved knowledge of disease etiology;
however, there remains the need for better understanding of the genetic factors that can
modify CDA disease severity. One of the major advantages of the NGS approach is the
identification of both the polygenic conditions and the modifier variants associated with
causative mutations. In a recent study, an analysis of patients with CDA type II that used a
target panel of 81 genes for modifier genes identified modifier variants that could explain the
clinical variability of these patients, and even among patients who shared the same
pathogenic variants. Among these variants, an ERFE gene recurrent low-frequency variant,
p.A260S, was shown in 12.5% of patients with CDAII who had severe phenotypes. ERFE
encodes erythroferrone, which is a soluble protein that is secreted by erythroid precursors
and that suppresses expression of hepcidin. Increased levels of ERFE are associated with the
ERFE-A260S variant, which results in large impairment of the regulation pathways for iron at
the level of the liver. ERFE-A260S functional characterization in a hepatic cell system showed
that it has a modifier role in iron overload through the BMP/SMAD pathway. This was the first
description of ERFE polymorphism as a genetic modifier variant.
Email address: roberta.russo@unina.it
References
1. Iolascon A, Esposito MR, Russo R. Clinical aspects and pathogenesis of congenital dyserythropoietic
anemias: from morphology to molecular approach. Haematologica. 2012;97(12):1786-94.
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1283.
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dyserythropoietic anemias. Expert review of hematology. 2016;9(3):283-96.
4. Russo R, Andolfo I, Manna F, et al. Increased levels of ERFE-encoding FAM132B in patients with
congenital dyserythropoietic anemia type II. Blood. 2016;128(14):1899-1902.
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SCIENTIFIC PROGRAMME
SESSION I
BONE MARROW
RESPONSE TO VIRAL
INFECTIONS
SESSION II
HAEMATOLOGICAL
RESPONSE TO SARS
COV2 INFECTION
SESSION III
DYSERYTHROPOIESIS IN
CLONAL HAEMOPOIESIS
AND MDS
SESSION IV
ERYTHROPOIESIS
CONTROL
SESSION V
ERYTHROPOIESIS
CONTROL : PHASE 2
SESSION VI
IRON METABOLISM
AND ERYTHROPOIESIS
SESSION VII
INHERITED
DYSERYTHROPOIESIS
SESSION VIII
GENE THERAPY/EDITION
SESSION IX – DRUGS
AND INEFFECTIVE
ERYTHROPOIESIS
SELECTED ABSTRACTS
FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FOR A POSTER
PRESENTATION
FACULTY DISCLOSURES