Frameshift mutation in p53 regulator RPL26 is associated with multiple physical abnormalities and a specific pre-rRNA processing defect in Diamond-Blackfan anemia. - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Human Mutation Année : 2012

Frameshift mutation in p53 regulator RPL26 is associated with multiple physical abnormalities and a specific pre-rRNA processing defect in Diamond-Blackfan anemia.

Stella M Davies
  • Fonction : Auteur
Leana Doherty
  • Fonction : Auteur
Roxanne Ghazvinian
  • Fonction : Auteur
Colin A Sieff
  • Fonction : Auteur
Peter E Newburger
  • Fonction : Auteur
Edyta Niewiadomska
  • Fonction : Auteur
Michal Matysiak
  • Fonction : Auteur
Bertil Glader
  • Fonction : Auteur
Jeffrey M Lipton
  • Fonction : Auteur
Alan H Beggs
  • Fonction : Auteur

Résumé

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.

Dates et versions

hal-00688367 , version 1 (17-04-2012)

Identifiants

Citer

Hanna T Gazda, Milena Preti, Mee Rie Sheen, Marie-Françoise O'Donohue, Adrianna Vlachos, et al.. Frameshift mutation in p53 regulator RPL26 is associated with multiple physical abnormalities and a specific pre-rRNA processing defect in Diamond-Blackfan anemia.. Human Mutation, 2012, epub ahead of print. ⟨10.1002/humu.22081⟩. ⟨hal-00688367⟩
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