High frequency of ribosomal protein gene deletions in Italian Diamond-Blackfan anemia patients detected by multiplex ligation-dependent probe amplification assay

Paola Quarello, Emanuela Garelli, Alfredo Brusco, Adriana Carando, Cecilia Mancini, Patrizia Pappi, Luciana Vinti, Johanna Svahn, Irma Dianzani, Ugo Ramenghi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1813-1817
Number of pages5
JournalHaematologica
Volume97
Issue number12
DOIs
Publication statusPublished - Dec 1 2012

Keywords

  • Diamond-blackfan anemia
  • Multiplex ligationdependent probe amplification
  • Ribosomal protein gene deletion

ASJC Scopus subject areas

  • Hematology

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