Diamond-Blackfan anemia is an autosomal dominant disease due to mutations in 
nine ribosomal protein encoding genes. Because most mutations are loss of 
function and detected by direct sequencing of coding exons, we reasoned that 
part of the approximately 50% mutation negative patients may have carried a copy 
number variant of ribosomal protein genes. As a proof of concept, we designed a 
multiplex ligation-dependent probe amplification assay targeted to screen the 
six genes that are most frequently mutated in Diamond-Blackfan anemia patients: 
RPS17, RPS19, RPS26, RPL5, RPL11, and RPL35A. Using this assay we showed that 
deletions represent approximately 20% of all mutations. The combination of 
sequencing and multiplex ligation-dependent probe amplification analysis of 
these six genes allows the genetic characterization of approximately 65% of 
patients, showing that Diamond-Blackfan anemia is indisputably a ribosomopathy.