ClinGen Dosage Sensitivity Curation Page

2p15p16.1 region (includes BCL11A)

Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
16963482 Rajcan-Separovic et al (2007) described two unrelated individuals with similar de novo interstitial microdeletions at 2p15-2p16.1 of 4.5 and 5.7Mb, identified on a 1Mb resolution BAC array. A similar clinical phenotype was noted, including moderate to severe intellectual disability, autism/autistic features, microcephaly, structural brain anomalies including cortical dysplasia/pachygyria, renal anomalies, digital camptodactyly, visual impairment, strabismus, neuromotor deficits, communication and attention impairments, and a distinctive pattern of craniofacial features.
18245392 de Leeuw et al. (2008) report a 32-year-old male with a de novo, mosaic (20/30 cells analyzed) 3.9 Mb loss at 2p15p16.1. The authors report that their patient's deletion falls within those of the two patients reported by Rajcan-Separovic et al., and that he displays similar clinical features, including intellectual disability, microcephaly, optic nerve hypoplasia, hydronephrosis, feeding problems, and some dysmorphic facial features.
22579565 Hucthagowder et al. (2012) report a de novo 2.5 Mb deletion of 2p15p16.1 in a female infant with features similar to those of other reported patients, including developmental delays, microcephaly, dysmorphic features, and renal anomalies. These authors also propose a 1.1 Mb critical region for overlapping phenotypic features observed in this syndrome. This paper provides a summary of features observed in patients reported at the time of publication and graphic illustrating the regions of overlap between the cases. The authors review previously reported cases, including a smaller, nested deletion (originally reported by Chabchoub et al. 2008); however, this patient has fewer overlapping phenotypic features with the other reported cases.

Evidence for Triplosenstive Phenotype

Evidence for triplosensitivity phenotype
PubMed ID Description
22726847 Luo et al (2012) identified a de novo 1.7Mb duplication in 2p15 in one proband with autism with significant gene-expression alteration of XPO1 in an analysis of 244 families with discordant siblings in the Simons Simplex Collection.
26278498 Authors describe a patient with a de novo 1665 kb microduplication of the 2p15p16.1 region a male with mild global developmental delay and the absence of autistic behaviors. In Decipher, Patients 257648 and 258333 have a 2.4 Mb gain and 2 Mb gain, respectively. Patients 265052 and 1570 have 1.2 Mb gain and 0.9 Mb gain, respectively. All four patients have an abnormal developmental phenotype and the duplication has been found to be de novo.

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.