TY - JOUR
TI - Frameshift mutation in p53 regulator RPL26 is associated with multiple physical abnormalities and a specific pre-ribosomal RNA processing defect in diamond-blackfan anemia
AU - Gazda, H.T.
AU - Preti, M.
AU - Sheen, M.R.
AU - O'Donohue, M.-F.
AU - Vlachos, A.
AU - Davies, S.M.
AU - Kattamis, A.
AU - Doherty, L.
AU - Landowski, M.
AU - Buros, C.
AU - Ghazvinian, R.
AU - Sieff, C.A.
AU - Newburger, P.E.
AU - Niewiadomska, E.
AU - Matysiak, M.
AU - Glader, B.
AU - Atsidaftos, E.
AU - Lipton, J.M.
AU - Gleizes, P.-E.
AU - Beggs, A.H.
JO - Human Mutation
PY - 2012
VL - 33
TODO - 7
SP - 1037-1044
PB - 
SN - 1059-7794, 1098-1004
TODO - 10.1002/humu.22081
TODO - genomic DNA;  nucleotide;  protein p53;  ribosome protein;  ribosome protein l19;  ribosome protein l26;  ribosome protein l3;  small interfering RNA;  unclassified drug, article;  biogenesis;  Blackfan Diamond anemia;  controlled study;  female;  frameshift mutation;  gene deletion;  gene sequence;  genetic variability;  human;  human cell;  major clinical study;  missense mutation;  newborn;  nucleotide sequence;  physical disease;  priority journal;  protein analysis;  ribosome;  RNA processing, Abnormalities, Multiple;  Anemia, Diamond-Blackfan;  Blotting, Northern;  Blotting, Western;  Frameshift Mutation;  HeLa Cells;  Humans;  Ribosomal Proteins;  RNA, Ribosomal;  RNA, Small Interfering;  Tumor Suppressor Protein p53
TODO - 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. © 2012 Wiley-Liss, Inc.
ER -