Identification of a new in-frame deletion of six amino acids in ribosomal protein S19 in a patient with Diamond-Blackfan anemia

Ribosomal protein S19 (RPS19) is currently the only gene associated with Diamond-Blackfan anemia (DBA), a rare congenital pure red cell aplasia characterized by normochromic macrocytic anemia, reticulocytopenia, and normocellular bone marrow with a selective deficiency of erythroid precursors. RPS19 is mutated in 25% of DBA patients, but its role in DBA pathogenesis remains elusive. We have identified a novel heterozygous microdeletion in RPS19 in a DBA patient presenting with profound anemia after birth. The deletion of 18 nucleotides (233–250; A in start codon is +1) in exon 4 leads to the elimination of 6 amino acids 78IYGGRQ83, affecting the most conserved stretch of three amino acids (YGG) in RPS19. The mutated allele was not detected in the patientʹs family members, indicating de novo mutation. Both alleles were expressed at the same level. Using an immunofluorescence technique, the mutated RPS19 protein localized to nucleoli, and its intracellular distribution did not differ from the wild-type RPS19. The deletion of only a few amino acids of this protein with a preserved reading frame is rare, and this type of a mutation could be very helpful in further experiments to define the role of the RPS19 protein in DBA pathogenesis.