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Haploinsufficiency of RPS14 in 5q− syndrome is associated with deregulation of ribosomal‐ and translation‐related genes
Author(s) -
Pellagatti Andrea,
HellströmLindberg Eva,
Giagounidis Aristoteles,
Perry Janet,
Malcovati Luca,
Della Porta Matteo G.,
Jädersten Martin,
Killick Sally,
Fidler Carrie,
Cazzola Mario,
Wainscoat James S.,
Boultwood Jacqueline
Publication year - 2008
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2008.07178.x
Subject(s) - ribosome biogenesis , haploinsufficiency , ribosomal protein , ribosome , ribosomal rna , biology , translation (biology) , genetics , gene , microbiology and biotechnology , messenger rna , rna , phenotype
Summary We have previously demonstrated haploinsufficiency of the ribosomal gene RPS14 , which is required for the maturation of 40S ribosomal subunits and maps to the commonly deleted region, in the 5q− syndrome. Patients with Diamond‐Blackfan anaemia (DBA) show haploinsufficiency of the closely related ribosomal protein RPS19, and show a consequent downregulation of multiple ribosomal‐ and translation‐related genes. By analogy with DBA, we have investigated the expression profiles of a large group of ribosomal‐ and translation‐related genes in the CD34 + cells of 15 myelodysplastic syndrome (MDS) patients with 5q− syndrome, 18 MDS patients with refractory anaemia (RA) and a normal karyotype, and 17 healthy controls. In this three‐way comparison, 55 of 579 ribosomal‐ and translation‐related probe sets were found to be significantly differentially expressed, with approximately 90% of these showing lower expression levels in the 5q− syndrome patient group. Using hierarchical clustering, patients with the 5q− syndrome could be separated both from other patients with RA and healthy controls solely on the basis of the deregulated expression of ribosomal‐ and translation‐related genes. Patients with the 5q− syndrome have a defect in the expression of genes involved in ribosome biogenesis and in the control of translation, suggesting that the 5q− syndrome represents a disorder of aberrant ribosome biogenesis.