ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000002.11) (NC_000002.12)
Evidence for haploinsufficiency phenotype
PubMed ID Description
27453576 Dias et al (2016) report a unique de novo variant in the BCL11A gene in each of nine individuals with intellectual disability, strabismus, persistence of fetal hemoglobin, and other findings such as joint hypermobility, behavior abnormalities, facial dysmorphism and microcephaly (three missense, three nonsense, and three frameshift). Two of the nonsense variants were in exon 2 of this 4-5 exon gene (depending on transcript). Variants were detected by whole exome sequencing. Functional studies of missense mutations were consistent with loss of function and haploinsufficiency of Bcl11a in mice causes impaired cognition and behavior and microcephaly.
25938782 Basak et al (2015) found BCL11A as the only gene in the smallest region of overlap in three patients with different de novo deletions from 2p15 to 2p16.1, autism, hypotonia, facial dysmorphism, developmental delay, and persistent fetal hemoglobin. Deletions were detected by aCGH.
25979662 Balci et al (2015) report a de novo 0.875 Mb deletion encompassing only BCL11A detected by aCGH in a patient with developmental delay, brain malformations, and dysmorphic features. The entire BCL11A gene is included in the deleted interval and no other significant CNVs were observed in this patient.

Haploinsufficiency phenotype comments:

Loss of function changes in the BCL11A gene cause developmental delay, dysmorphic features, and persistent fetal hemoglobin. Additional publication, PMID 24810580: Peter et al (2014) report a de novo 0.2 Mb deletion containing only the BCL11A gene in a patient with speech apraxia and dysarthria, gross motor apraxia, hypotonia, and mild intellectual disability. Array CGH also detected two small duplications of unknown inheritance in this patient.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

No reports of duplications involving only BCL11A