title: Clinical and molecular variability in congenital dyserythropoietic anaemia type I.
abstract: Congenital dyserythropoietic anaemia (CDA) type I is a rare, inherited disorder characterised by ineffective erythropoiesis and macrocytic anaemia. Complex bone disease has only occasionally been associated with this disease. CDA I is caused by mutations in the CDAN1 gene encoding for codanin-1. Our aim was to characterise the CDAN1 mutation in eight unrelated patients with sporadic CDA I, three of whom had complex bone disease. Six novel mutations in the CDAN1 gene were identified. In two patients, one mutation and in another, both mutations were elusive. No patient was homozygous for a null-type mutation. However, one patient with complex bone disease was homozygous for a splice-site mutation (IVS-12+5G>A). Western blotting revealed that codanin-1 synthesis was 65% less than the control. Five single nucleotide polymorphisms (SNPs) previously unreported in the literature or the SNP database were also identified. Although the absence of codanin-1 is probably lethal, the presence of 35% of the protein was compatible with life but was associated with severe clinical manifestations. However, in most patients studied, no correlation could be established between the expected levels of codanin-1 or the nature of the mutation and the severity of the clinical manifestations.
authors.affiliation: Paediatric Haematology Laboratory, Felsenstein Medical Research Centre, Beilinson Campus, Petah Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Israel. htamary@post.tau.ac.il
authors.forename: Hannah
authors.initials: H
authors.lastname: Tamary
authors.forename: Orly
authors.initials: O
authors.lastname: Dgany
authors.forename: Alexis
authors.initials: A
authors.lastname: Proust
authors.forename: Tatyana
authors.initials: T
authors.lastname: Krasnov
authors.forename: Nili
authors.initials: N
authors.lastname: Avidan
authors.forename: Tal
authors.initials: T
authors.lastname: Eidelitz-Markus
authors.forename: Gil
authors.initials: G
authors.lastname: Tchernia
authors.forename: David
authors.initials: D
authors.lastname: Geneviève
authors.forename: Valérie
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bader-Meunier
authors.forename: Corinne
authors.initials: C
authors.lastname: Ferrero-Vacher
authors.forename: Martine
authors.initials: M
authors.lastname: Munzer
authors.forename: Ralph
authors.initials: R
authors.lastname: Gruppo
authors.forename: Eithan
authors.initials: E
authors.lastname: Fibach
authors.forename: Osnat
authors.initials: O
authors.lastname: Konen
authors.forename: Isaac
authors.initials: I
authors.lastname: Yaniv
authors.forename: Jean
authors.initials: J
authors.lastname: Delaunay
mesh_terms: D000293:Adolescent; D000328:Adult; D000742:Anemia, Dyserythropoietic, Congenital / Q000150:complications / Q000235:genetics*; D015153:Blotting, Western / Q000379:methods; D001847:Bone Diseases / Q000150:complications / Q000235:genetics; D002648:Child; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004252:DNA Mutational Analysis; D005838:Genotype; D006023:Glycoproteins / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007223:Infant; D017880:Limb Deformities, Congenital / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins; D010641:Phenotype
chemical_list: C470477:CDAN1 protein, human; D006023:Glycoproteins; D009687:Nuclear Proteins