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RPS19 mutations in patients with Diamond‐Blackfan anemia
Author(s) -
Campagnoli Maria Francesca,
Ramenghi Ugo,
Armiraglio Marta,
Quarello Paola,
Garelli Emanuela,
Carando Adriana,
Avondo Federica,
Pavesi Elisa,
Fribourg Sébastien,
Gleizes PierreEmmanuel,
Loreni Fabrizio,
Dianzani Irma
Publication year - 2008
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20752
Subject(s) - diamond–blackfan anemia , anemia , medicine , mutation , genetics , diamond , pediatrics , biology , gene , chemistry , rna , organic chemistry , ribosome
Diamond‐Blackfan anemia (DBA) is an inherited disease characterized by pure erythroid aplasia. Thirty percent (30%) of patients display malformations, especially of the hands, face, heart, and urogenital tract. DBA has an autosomal dominant pattern of inheritance. De novo mutations are common and familial cases display wide clinical heterogeneity. Twenty‐five percent (25%) of patients carry a mutation in the ribosomal protein (RP) S19 gene, whereas mutations in RPS24, RPS17, RPL35A, RPL11, and RPL5 are rare. These genes encode for structural proteins of the ribosome. A link between ribosomal functions and erythroid aplasia is apparent in DBA, but its etiology is not clear. Most authors agree that a defect in protein synthesis in a rapidly proliferating tissue, such as the erythroid bone marrow, may explain the defective erythropoiesis. A total of 77 RPS19 mutations have been described. Most are whole gene deletions, translocations, or truncating mutations (nonsense or frameshift), suggesting that haploinsufficiency is the basis of DBA pathology. A total of 22 missense mutations have also been described and several works have provided in vitro functional data for the mutant proteins. This review looks at the data on all these mutations, proposes a functional classification, and describes six new mutations. It is shown that patients with RPS19 mutations display a poorer response to steroids and a worse long‐term prognosis compared to other DBA patients. Hum Mutat 29(7), 911–920, 2008. © 2008 Wiley‐Liss, Inc.