title: New Codanin-1 Gene Mutations in a Italian Patient with Congenital Dyserythropoietic Anemia Type I and Heterozygous Beta-Thalassemia.
abstract: Congenital dyserythropoietic anemia type I is an autosomal recessive disorder associated with macrocytic anemia, ineffective erythropoiesis, iron overloading and characterized by abnormal chromatin ultrastructure in erythroblasts such as internuclear chromatin bridges, spongy heterochromatin and invagination of the nuclear membrane. A 58-year-old Causasian man with chronic hemolytic anemia, heterozygous for β (+) -globin IVS1, nt110 G>A mutation (causing abnormal alpha:beta globin chain ratio) showed clinical, laboratory and hematological features suggesting diagnosis of CDA1. Sequence analysis of CDA-related genes revealed compound heterozygosity for two novel mutations in the CDAN1 gene: a frameshift mutation 3367 del 4 (TTAG) in exon 25 and a missense mutation c.1811 G>T in exon 11 causing an aminoacid change from glycine to valine at codon 565 (G565V). One of the propositus' brothers showed the same gene mutations. As the CDA1 can mimic thalassemia, a frequent misdiagnosis is possible especially in countries where the prevalence of thalassemia is high. A strong clinical suspicion in patients who do not reveal a clear genetic basis for presumed thalassemia may help clinch the correct diagnosis.
authors.affiliation: Ospedale V. Cervello UOC Ematologia per le Malattie Rare del Sangue e degli Organi Ematopoietici, Azienda Ospedali Riuniti Villa Sofia-Cervello, Via Trabucco n° 180, 90146 Palermo, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: D'Alcamo
authors.affiliation: Ospedale V. Cervello UOC Ematologia per le Malattie Rare del Sangue e degli Organi Ematopoietici, Azienda Ospedali Riuniti Villa Sofia-Cervello, Via Trabucco n° 180, 90146 Palermo, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Agrigento
authors.affiliation: Ospedale V. Cervello UOC Ematologia per le Malattie Rare del Sangue e degli Organi Ematopoietici, Azienda Ospedali Riuniti Villa Sofia-Cervello, Via Trabucco n° 180, 90146 Palermo, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Pitrolo
authors.affiliation: Ospedale V. Cervello UOC Ematologia per le Malattie Rare del Sangue e degli Organi Ematopoietici, Azienda Ospedali Riuniti Villa Sofia-Cervello, Via Trabucco n° 180, 90146 Palermo, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Sclafani
authors.affiliation: Ospedale V. Cervello UOC Ematologia per le Malattie Rare del Sangue e degli Organi Ematopoietici, Azienda Ospedali Riuniti Villa Sofia-Cervello, Via Trabucco n° 180, 90146 Palermo, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Barone
authors.affiliation: Ospedale V. Cervello UOC Ematologia per le Malattie Rare del Sangue e degli Organi Ematopoietici, Azienda Ospedali Riuniti Villa Sofia-Cervello, Via Trabucco n° 180, 90146 Palermo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Calvaruso
authors.affiliation: Ospedale V. Cervello UOC Ematologia per le Malattie Rare del Sangue e degli Organi Ematopoietici, Azienda Ospedali Riuniti Villa Sofia-Cervello, Via Trabucco n° 180, 90146 Palermo, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Buffa
authors.affiliation: Ospedale V. Cervello UOC Ematologia per le Malattie Rare del Sangue e degli Organi Ematopoietici, Azienda Ospedali Riuniti Villa Sofia-Cervello, Via Trabucco n° 180, 90146 Palermo, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Maggio
keywords: CDAN1 gene; Congenital dyserythropoietic anemia; Ineffective erythropoiesis; Internuclear chromatin bridges