The Czech National Diamond-Blackfan Anemia Registry: Clinical data and ribosomal protein mutations update

• Published in: Blood cells, molecules, & diseases molecules, & diseases, 2012-04, Vol.48 (4), p.209-218
• Main Authors: Pospisilova, Dagmar, Cmejlova, Jana, Ludikova, Barbora, Stary, Jan, Cerna, Zdena, Hak, Jiri, Timr, Pavel, Petrtylova, Kvetoslava, Blatny, Jan, Vokurka, Samuel, Cmejla, Radek
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Anemia, Diamond-Blackfan - diagnosis; Anemia, Diamond-Blackfan - epidemiology; Anemia, Diamond-Blackfan - genetics; Child; Child, Preschool; Czech Republic - epidemiology; Exons; Female; Gene Order; Genetic Association Studies; Humans; Incidence; Infant; Male; Middle Aged; Mutation; Phenotype; Registries; Ribosomal Proteins - genetics; Young Adult
• ISSN: 1079-9796; 1096-0961
• DOI: 10.1016/j.bcmd.2012.02.002

Diamond-Blackfan anemia is a rare inherited bone marrow failure syndrome diagnosed in early infancy that is characterized by a (a) macrocytic anemia with no other significant cytopenia, (b) reticulocytopenia, and (c) normal bone marrow cellularity with a paucity of erythroid precursors. Physical anomalies are often present. Mutations in several ribosomal proteins have been associated with the disease. Here we present a detailed description of 39 patients from 34 families enrolled in the Czech National Diamond-Blackfan Anemia Registry. Erythrocyte adenosine deaminase activity and serum erythropoietin levels were measured and bone marrow analysis and clonogenic assays were carried out. Twenty-two different ribosomal proteins were sequenced. We identified mutations in five different ribosomal proteins in 28/39 patients (71.8%) from 23/34 families (67.6%). Several new mutations are described. The most interesting data relate to genotype–phenotype correlations. All patients with ribosomal protein L5 or ribosomal protein L11 mutations have a thumb defect usually with one or more other anomalies. Most of these patients were born small for gestational age and currently have short stature. We also described five patients with a ribosomal protein S26 mutation. All of the latter are transfusion-dependent and they exhibit skeletal abnormalities rather than thumb or craniofacial deformities. Patients with ribosomal protein S19 seem to bear mildest associated anomalies, usually in a craniofacial region.