Blood, 15 January 2001, Vol. 97, No. 2, pp. 579-580
CORRESPONDENCE
To the editor:
Ribosomal proteins S3a, S13, S16, and S24 are not
mutated in patients with Diamond-Blackfan anemia
Considerable effort has been invested in identification of
a gene responsible for Diamond-Blackfan anemia (DBA). The disorder is
characterized by red cell hypoplasia presenting in early infancy and
is accompanied in about 40% of the patients by various
physical anomalies (for review see Willig et al1).
Ribosomal protein S19 (RPS19) was identified as a candidate gene for
DBA and mutations in this gene have been described in 25% of DBA
patients.2,3 However, the mechanism by which mutations in
RPS19 can lead to DBA remains unclear.
RPS19 is a structural component of a small ribosomal subunit and is
known to have two other functions. First, RPS19 homodimers are released
by apoptotic cells and act as a chemotactic factor for monocytes during
macrophage-dependent apoptotic cell clearance.4 Second,
RPS19, together with ribosomal proteins S3a, S13, S16, and S24,
participates in the binding of eukaryotic initiation factor 2 (eIF-2)
to ribosomes.5 eIF-2 plays a central role in the
initiation of translation, and its function is controlled in an
erythroid-specific manner by heme-regulated kinase.6 To
investigate the possibility that DBA phenotype might result from
mutations in ribosomal proteins involved in eIF-2 binding, we sequenced
cDNAs for RPS3a, S13, S16, and S24 in 14 patients from the Czech
National DBA Registry. Five of these patients have been previously
shown to carry a mutation in the RPS19 gene.7
After obtaining informed consent, total RNA was isolated from
peripheral blood mononuclear cells, and reverse transcription was
performed using an oligo(dT) primer. Primers specific for full-length
coding regions of RPS3a, S13, S16, and S24 were used for PCR
amplification. PCR products were sequenced on an automated genetic
analyzer, and resulting sequences were evaluated for the presence of mutations.
In all DBA patients tested, no mutations in RPS3a, S13, S16, and S24
were found on the cDNA level. We therefore conclude that these four of
the five ribosomal proteins important for eIF-2 binding to ribosomes
are not involved in DBA pathogenesis.
Radek Cmejla, Jana Blafkova, Tomas Stopka, and Jaroslav Jelinek
Institute of Hematology and Blood Transfusion, Prague, Czech
Republic
Kveta Petrtylova
Department of Hematology, Second Faculty of Medicine Charles
University, Prague, Czech Republic
Dagmar Pospisilova
Department of Pediatrics, Faculty of Medicine Palacky
University and Faculty Hospital, Olomouc, Czech Republic
Acknowledgments
Supported by the Czech Ministry of Health grant CEZMZ 0023736001.
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