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The ribosomal basis of diamond‐blackfan anemia: mutation and database update
Author(s) -
Boria Ilenia,
Garelli Emanuela,
Gazda Hanna T.,
Aspesi Anna,
Quarello Paola,
Pavesi Elisa,
Ferrante Daniela,
Meerpohl Joerg J.,
Kartal Mutlu,
Da Costa Lydie,
Proust Alexis,
Leblanc Thierry,
Simansour Maud,
Dahl Niklas,
Fröjmark AnneSophie,
Pospisilova Dagmar,
Cmejla Radek,
Beggs Alan H.,
Sheen Mee R.,
Landowski Michael,
M. Buros Christopher,
M. Clinton Catherine,
J. Dobson Lori,
Vlachos Adrianna,
Atsidaftos Eva,
Lipton Jeffrey M.,
Ellis Steven R.,
Ramenghi Ugo,
Dianzani Irma
Publication year - 2010
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.21383
Subject(s) - biology , genetics , pseudogene , diamond–blackfan anemia , mutation , gene , penetrance , phenotype , mutagenesis , ribosome , rna , genome
Diamond‐Blackfan Anemia (DBA) is characterized by a defect of erythroid progenitors and, clinically, by anemia and malformations. DBA exhibits an autosomal dominant pattern of inheritance with incomplete penetrance. Currently nine genes, all encoding ribosomal proteins (RP), have been found mutated in approximately 50% of patients. Experimental evidence supports the hypothesis that DBA is primarily the result of defective ribosome synthesis. By means of a large collaboration among six centers, we report here a mutation update that includes nine genes and 220 distinct mutations, 56 of which are new. The DBA Mutation Database now includes data from 355 patients. Of those where inheritance has been examined, 125 patients carry a de novo mutation and 72 an inherited mutation. Mutagenesis may be ascribed to slippage in 65.5% of indels, whereas CpG dinucleotides are involved in 23% of transitions. Using bioinformatic tools we show that gene conversion mechanism is not common in RP genes mutagenesis, notwithstanding the abundance of RP pseudogenes. Genotype–phenotype analysis reveals that malformations are more frequently associated with mutations in RPL5 and RPL11 than in the other genes. All currently reported DBA mutations together with their functional and clinical data are included in the DBA Mutation Database. Hum Mutat 31:1269–1279, 2010. © 2010 Wiley‐Liss, Inc.