title: Whole exome sequencing in the differential diagnosis of Diamond-Blackfan anemia: Clinical and molecular study of three patients with novel RPL5 and mosaic RPS19 mutations.
abstract: Diamond-Blackfan anemia (DBA) is a rare congenital disorder presenting remarkable phenotypic overlap with other inherited bone marrow failure syndromes, making differential diagnosis challenging and its confirmation often reached with great delay. By whole exome sequencing, we unraveled the presence of pathogenic variants affecting genes already known to be involved in DBA pathogenesis (RPL5 and RPS19) in three patients with otherwise uncertain clinical diagnosis, and provided new insights on DBA genotype-phenotype correlations. Remarkably, the RPL5 c.482del frameshift mutation has never been reported before, whereas the RPS19 c.3G>T missense mutation, although previously described in a 2-month-old DBA patient without malformations and refractory to steroid therapy, was detected here in the mosaic state in different bodily tissues for the first time in DBA patients.
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy. Electronic address: edoardo.errichiello01@universitadipavia.it.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Errichiello
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Vetro
authors.affiliation: Pediatric Hematology and Oncology, IRCCS Fondazione Policlinico S. Matteo, Pavia, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Mina
authors.affiliation: Genetic Counseling Service, Department of Pediatrics, Regional Hospital of Bolzano, Bolzano, Italy; Unit of Medical Genetics, University of Bologna, Bologna, Italy.
authors.forename: Anita
authors.initials: A
authors.lastname: Wischmeijer
authors.affiliation: Unit of Molecular Pathology, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, (Torino), Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Berrino
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy; IRCCS Fondazione Policlinico S. Matteo, Pavia, Italy.
authors.forename: Miriam
authors.initials: M
authors.lastname: Carella
authors.affiliation: Unit of Medical Genetics, University of Bologna, Bologna, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Romagnoli
authors.affiliation: Unit of Pediatrics, Ospedale Infermi di Rimini, Rimini, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Sacchini
authors.affiliation: Unit of Molecular Pathology, Candiolo Cancer Institute, FPO-IRCCS, Candiolo, (Torino), Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Venesio
authors.affiliation: Pediatric Hematology and Oncology, IRCCS Fondazione Policlinico S. Matteo, Pavia, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Zecca
authors.affiliation: Department of Molecular Medicine, University of Pavia, Pavia, Italy.
authors.forename: Orsetta
authors.initials: O
authors.lastname: Zuffardi
mesh_terms: D029503:Anemia, Diamond-Blackfan / Q000175:diagnosis / Q000235:genetics; D002675:Child, Preschool; D003937:Diagnosis, Differential; D059472:Exome; D005260:Female; D016368:Frameshift Mutation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008297:Male; D009030:Mosaicism; D020125:Mutation, Missense; D012269:Ribosomal Proteins / Q000235:genetics*
chemical_list: D012269:Ribosomal Proteins; C549166:ribosomal protein L5, human; C040343:ribosomal protein S19
keywords: Diamond-Blackfan anemia; Inherited bone marrow failure syndromes; Mosaicism; RPL5; RPS19; Whole exome sequencing