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Frameshift mutation in p53 regulator RPL26 is associated with multiple physical abnormalities and a specific pre‐ribosomal RNA processing defect in diamond–blackfan anemia
Author(s) -
Gazda Hanna T.,
Preti Milena,
Sheen Mee Rie,
O'Donohue MarieFrançoise,
Vlachos Adrianna,
Davies Stella M.,
Kattamis Antonis,
Doherty Leana,
Landowski Michael,
Buros Christopher,
Ghazvinian Roxanne,
Sieff Colin A.,
Newburger Peter E.,
Niewiadomska Edyta,
Matysiak Michal,
Glader Bertil,
Atsidaftos Eva,
Lipton Jeffrey M.,
Gleizes PierreEmmanuel,
Beggs Alan H.
Publication year - 2012
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.22081
Subject(s) - biology , diamond–blackfan anemia , proband , frameshift mutation , genetics , missense mutation , gene , ribosome biogenesis , ribosomal rna , ribosomal protein , mutation , ribosome , microbiology and biotechnology , rna
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 RP regulating p53 activity that is linked to DBA. Hum Mutat 33:1037–1044, 2012. © 2012 Wiley Periodicals, Inc.