Mutations in the 5′ UTR of ANKRD26, the ankirin repeat domain 26 gene, cause an autosomal-dominant form of inherited thrombocytopenia, THC2

Tommaso Pippucci, Anna Savoia, Silverio Perrotta, Núria Pujol-Moix, Patrizia Noris, Giovanni Castegnaro, Alessandro Pecci, Chiara Gnan, Francesca Punzo, Caterina Marconi, Samuele Gherardi, Giuseppe Loffredo, Daniela De Rocco, Saverio Scianguetta, Serena Barozzi, Pamela Magini, Valeria Bozzi, Luca Dezzani, Mariateresa Di Stazio, Marcella FerraroGiovanni Perini, Marco Seri, Carlo L. Balduini

Research output: Contribution to journalArticle

Abstract

THC2, an autosomal-dominant thrombocytopenia described so far in only two families, has been ascribed to mutations in MASTL or ACBD5. Here, we show that ANKRD26, another gene within the THC2 locus, and neither MASTL nor ACBD5, is mutated in eight unrelated families. ANKRD26 was also found to be mutated in the family previously reported to have an ACBD5 mutation. We identified six different ANKRD26 mutations, which were clustered in a highly conserved 19 bp sequence located in the 5′ untranslated region. Mutations were not detected in 500 controls and are absent from the 1000 Genomes database. Available data from an animal model and Dr. Watson's genome give evidence against haploinsufficiency as the pathogenetic mechanism for ANKRD26-mediated thrombocytopenia. The luciferase reporter assay suggests that these 5′ UTR mutations might enhance ANKRD26 expression. ANKRD26 is the ancestor of a family of primate-specific genes termed POTE, which have been recently identified as a family of proapoptotic proteins. Dysregulation of apoptosis might therefore be the pathogenetic mechanism, as demonstrated for another thrombocytopenia, THC4. Further investigation is needed to provide evidence supporting this hypothesis.

Original languageEnglish
Pages (from-to)115-120
Number of pages6
JournalAmerican Journal of Human Genetics
Volume88
Issue number1
DOIs
Publication statusPublished - Jan 7 2011

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Pippucci, T., Savoia, A., Perrotta, S., Pujol-Moix, N., Noris, P., Castegnaro, G., Pecci, A., Gnan, C., Punzo, F., Marconi, C., Gherardi, S., Loffredo, G., De Rocco, D., Scianguetta, S., Barozzi, S., Magini, P., Bozzi, V., Dezzani, L., Di Stazio, M., ... Balduini, C. L. (2011). Mutations in the 5′ UTR of ANKRD26, the ankirin repeat domain 26 gene, cause an autosomal-dominant form of inherited thrombocytopenia, THC2. American Journal of Human Genetics, 88(1), 115-120. https://doi.org/10.1016/j.ajhg.2010.12.006