title: The Czech National Diamond-Blackfan Anemia Registry: clinical data and ribosomal protein mutations update.
abstract: 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.
authors.affiliation: Department of Paediatrics, Palacky University, Olomouc, Czech Republic. dagmar.pospisilova@fnol.cz
authors.forename: Dagmar
authors.initials: D
authors.lastname: Pospisilova
authors.forename: Jana
authors.initials: J
authors.lastname: Cmejlova
authors.forename: Barbora
authors.initials: B
authors.lastname: Ludikova
authors.forename: Jan
authors.initials: J
authors.lastname: Stary
authors.forename: Zdena
authors.initials: Z
authors.lastname: Cerna
authors.forename: Jiri
authors.initials: J
authors.lastname: Hak
authors.forename: Pavel
authors.initials: P
authors.lastname: Timr
authors.forename: Kvetoslava
authors.initials: K
authors.lastname: Petrtylova
authors.forename: Jan
authors.initials: J
authors.lastname: Blatny
authors.forename: Samuel
authors.initials: S
authors.lastname: Vokurka
authors.forename: Radek
authors.initials: R
authors.lastname: Cmejla
mesh_terms: D000293:Adolescent; D000328:Adult; D029503:Anemia, Diamond-Blackfan / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D018153:Czech Republic / Q000453:epidemiology; D005091:Exons; D005260:Female; D023061:Gene Order; D056726:Genetic Association Studies; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D012042:Registries; D012269:Ribosomal Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D012269:Ribosomal Proteins