RGD Reference Report - BCL11A deletions result in fetal hemoglobin persistence and neurodevelopmental alterations. - Rat Genome Database

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BCL11A deletions result in fetal hemoglobin persistence and neurodevelopmental alterations.

Authors: Basak, A  Hancarova, M  Ulirsch, JC  Balci, TB  Trkova, M  Pelisek, M  Vlckova, M  Muzikova, K  Cermak, J  Trka, J  Dyment, DA  Orkin, SH  Daly, MJ  Sedlacek, Z  Sankaran, VG 
Citation: Basak A, etal., J Clin Invest. 2015 Jun;125(6):2363-8. doi: 10.1172/JCI81163. Epub 2015 May 4.
RGD ID: 11099977
Pubmed: PMID:25938782   (View Abstract at PubMed)
PMCID: PMC4497765   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI81163   (Journal Full-text)

A transition from fetal hemoglobin (HbF) to adult hemoglobin (HbA) normally occurs within a few months after birth. Increased production of HbF after this period of infancy ameliorates clinical symptoms of the major disorders of adult beta-hemoglobin: beta-thalassemia and sickle cell disease. The transcription factor BCL11A silences HbF and has been an attractive therapeutic target for increasing HbF levels; however, it is not clear to what extent BCL11A inhibits HbF production or mediates other developmental functions in humans. Here, we identified and characterized 3 patients with rare microdeletions of 2p15-p16.1 who presented with an autism spectrum disorder and developmental delay. Moreover, these patients all exhibited substantial persistence of HbF but otherwise retained apparently normal hematologic and immunologic function. Of the genes within 2p15-p16.1, only BCL11A was commonly deleted in all of the patients. Evaluation of gene expression data sets from developing and adult human brains revealed that BCL11A expression patterns are similar to other genes associated with neurodevelopmental disorders. Additionally, common SNPs within the second intron of BCL11A are strongly associated with schizophrenia. Together, the study of these rare patients and orthogonal genetic data demonstrates that BCL11A plays a central role in silencing HbF in humans and implicates BCL11A as an important factor for neurodevelopment.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
schizophrenia  IAGP 11099977DNA:snps:multiple (human)RGD 
schizophrenia  ISOBCL11A (Homo sapiens)11099977; 11099977DNA:snps:multiple (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Abnormality of mental function  IAGP 11099977DNA:snps:multiple (human)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Bcl11a  (BCL11 transcription factor A)

Genes (Mus musculus)
Bcl11a  (BCL11 transcription factor A)

Genes (Homo sapiens)
BCL11A  (BCL11 transcription factor A)


Additional Information