2P15-p16.1 microdeletions encompassing and proximal to BCL11A are associated with elevated HbF in addition to neurologic impairment

Maria Piccione, Paolo Prontera, Alister P. W. Funnell, Sandra Stehling-Sun, Thalia Papayannopoulou, Francesca Masiello, Valentina Ottaviani, Fiorella Ciaffoni, Antonino Giambona, John A. Stamatoyannopoulos, Anna R. Migliaccio, Aurelio Maggio, Lilian Varricchio, Manuela Marra

Risultato della ricerca: Articlepeer review

46 Citazioni (Scopus)


Elevated fetal hemoglobin (HbF) ameliorates the clinical severity of hemoglobinopathies such as β-thalassemia and sickle cell anemia. Currently, the only curative approach for individuals under chronic transfusion/chelation support therapy is allogeneic stem cell transplantation. However, recent analyses of heritable variations in HbF levels have provided a new therapeutic target for HbF reactivation: the transcriptional repressor BCL11A. Erythroid-specific BCL11A abrogation is now actively being sought as a therapeutic avenue, but the specific impact of such disruption in humans remains to be determined. Although single nucleotide polymorphisms in BCL11A erythroid regulatory elements have been reported, coding mutations are scarcer. It is thus of great interest that patients have recently been described with microdeletions encompassing BCL11A. These patients display neurodevelopmental abnormalities, but whether they show increased HbF has not been reported. We have examined the hematological phenotype, HbF levels, and erythroid BCL11A expression in 3 such patients. Haploinsufficiency of BCL11A induces only partial developmental g-globin silencing. Of greater interest is that a patient with a downstream deletion exhibits reduced BCL11A expression and increased HbF. Novel erythroid-specific regulatory elements in this region may be required for normal erythroid BCL11A expression, whereas loss of separate elements in the developing brain may explain the neurological phenotype.
Lingua originaleEnglish
pagine (da-a)89-93
Numero di pagine5
Stato di pubblicazionePublished - 2015

All Science Journal Classification (ASJC) codes

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  • ???subjectarea.asjc.2400.2403???
  • ???subjectarea.asjc.2700.2720???
  • ???subjectarea.asjc.1300.1307???


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