Clinical and molecular variability in congenital dyserythropoietic anaemia type I.
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.
Tamary
Hannah
H
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
Dgany
Orly
O
Proust
Alexis
A
Krasnov
Tatyana
T
Avidan
Nili
N
Eidelitz-Markus
Tal
T
Tchernia
Gil
G
Geneviève
David
D
Cormier-Daire
Valérie
V
Bader-Meunier
Brigitte
B
Ferrero-Vacher
Corinne
C
Munzer
Martine
M
Gruppo
Ralph
R
Fibach
Eithan
E
Konen
Osnat
O
Yaniv
Isaac
I
Delaunay
Jean
J
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
C470477:CDAN1 protein, human; D006023:Glycoproteins; D009687:Nuclear Proteins