High frequency of ribosomal protein gene deletions in Italian Diamond-Blackfan anemia patients detected by multiplex ligation-dependent probe amplification assay.
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.
Pediatric Onco-Hematology, Regina Margherita Children's Hospital, Turin, Italy.
Paola
P
Quarello
Emanuela
E
Garelli
Alfredo
A
Brusco
Adriana
A
Carando
Cecilia
C
Mancini
Patrizia
P
Pappi
Luciana
L
Vinti
Johanna
J
Svahn
Irma
I
Dianzani
Ugo
U
Ramenghi
D029503:Anemia, Diamond-Blackfan / Q000235:genetics* / Q000473:pathology; D017353:Gene Deletion; D020440:Gene Duplication; D006801:Humans; D060885:Multiplex Polymerase Chain Reaction / Q000379:methods*; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D012042:Registries; D012269:Ribosomal Proteins / Q000235:genetics*
C489281:RPL35A protein, human; C489203:RPS26 protein, human; D012269:Ribosomal Proteins; C027624:ribosomal protein L11; C549166:ribosomal protein L5, human; C040343:ribosomal protein S19