Frameshift mutation in p53 regulatorRPL26is associated with multiple physical abnormalities and a specific pre-ribosomal RNA processing defect in diamond-blackfan anemia

Autor: Leana Doherty, Adrianna Vlachos, Eva Atsidaftos, Antonis Kattamis, Stella M. Davies, Michał Matysiak, Christopher Buros, Alan H. Beggs, Edyta Niewiadomska, Colin A. Sieff, Jeffrrey M. Lipton, Milena Preti, Michael Landowski, Marie-Françoise O'Donohue, Roxanne Ghazvinian, Pierre-Emmanuel Gleizes, Mee Rie Sheen, Hanna T. Gazda, Bertil Glader, Peter E. Newburger
Přispěvatelé: Laboratoire de biologie moléculaire eucaryote (LBME), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Division of Genetics and Program in Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, The Feinstein Institute for Medical Research, First department of Pediatrics, University of Athens School of Medicine, Laboratory of Human Genetics of Infectious Diseases, Cohen Children's Medical Center of New York, Hofstra University School of Medicine, Hofstra University [Hempstead], First Department of Paediatrics, Athens University, Thalassaemia Unit, 'Aghia Sofia' Children's Hospital
Rok vydání: 2012
Předmět:
Ribosomal Proteins
Proband
Ribosomopathy
Ribosomal Protein L3
[SDV]Life Sciences [q-bio]
Blotting
Western
Pure red cell aplasia
Biology
medicine.disease_cause
Article
Frameshift mutation
03 medical and health sciences
0302 clinical medicine
Ribosomal protein
Genetics
medicine
Humans
Missense mutation
Abnormalities
Multiple
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
RNA
Small Interfering
Diamond–Blackfan anemia
Frameshift Mutation
ComputingMilieux_MISCELLANEOUS
Genetics (clinical)
Anemia
Diamond-Blackfan
030304 developmental biology
0303 health sciences
Mutation
Blotting
Northern
medicine.disease
Molecular biology
3. Good health
RNA
Ribosomal
030220 oncology & carcinogenesis
Tumor Suppressor Protein p53
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
HeLa Cells
Zdroj: Human Mutation
Human Mutation, Wiley, 2012, 33 (7), pp.1037-1044. ⟨10.1002/humu.22081⟩
Human Mutation, Wiley, 2012, epub ahead of print. ⟨10.1002/humu.22081⟩
ISSN: 1059-7794
1098-1004
DOI: 10.1002/humu.22081
Popis: International audience; Diamond-Blackfan anemia (DBA) is an inherited form of pure red cell aplasia that usually presents in infancy or early childhood and is associated with congenital malformations in ∼30-50% of patients. DBA has been associated with mutations in nine ribosomal protein (RP) genes in about 53% of patients. We completed a large scale screen of 79 RP genes by sequencing 16 RP genes (RPL3, RPL7, RPL8, RPL10, RPL14, RPL17, RPL19, RPL23A, RPL26, RPL27, RPL35, RPL36A, RPL39, RPS4X, RPS4Y1, and RPS21) in 96 DBA probands. We identified a de novo two-nucleotide deletion in RPL26 in one proband associated with multiple severe physical abnormalities. This mutation gives rise to a remarkable ribosome biogenesis defect that affects maturation of both the small and the large subunits. We also found a deletion in RPL19 and missense mutations in RPL3 and RPL23A, which may be variants of unknown significance. Together with RPL5, RPL11, and RPS7, RPL26 is the fourth ribosomal protein regulating p53 activity that is linked to DBA.
Databáze: OpenAIRE
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