ClinGen Dosage Sensitivity Curation Page

1p36 terminal region (includes GABRD)

  • Curation Status: Complete
  • id: ISCA-37434
  • Date last evaluated: 2016-05-31
  • Issue Type: ClinGen Region Curation
  • ClinGen Haploinsufficiency Score: 3
  • ClinGen Triplosensitivity Score: 2

Location Information

Select assembly: (NC_000001.10) ()
Evidence for haploinsufficiency phenotype
PubMed ID Description
17918734 Describes a well defined syndrome and gives a good overview of previous publications. In this study 1500 cases were screened by microarray. The authors summarise the main clinical features observed, highlight candidate genes, the types of rearrangements observed and propose a variety of mechanisms for generating and stabilising terminal deletions.
18245432 Describes 60 patients with 1p36 deletion syndrome providing information on the common clinical findings associated with the disorder, as well as other aspects such as neurodevelopmental disability and other malformations frequently reported.
22766398 Identified smallest region of overlap and describe 2 patients who were found to have 'pure' 1p36 microduplication. The authors also discuss clinically relevant genes that map to the critical region.

Haploinsufficiency phenotype comments:

The coordinates of this region correspond to those of the distal critical region as described originally by Wu et al. (1999) and reported by in a review by Jordan et al. (2015) (PMID:26345236). Deletions within the 1p36 region vary in size, and there has been no firm correlation between deletion size and phenotypic severity (Heilstedt et al. 2003) (PMID: 12687501). Note that genes used as landmarks are not necessarily causative of the complete phenotype(s) associated with the region. Of note, the review by Jordan et al. (2015) (PMID: 26345236) provides an overview of "efforts to map and identify the genes and genomic regions that contribute to specific 1p36-related phenotypes," and discusses the presence of a possible proximal 1p36 critical regions. It is unclear whether or not deletions of this proximal region constitutes a distinct phenotype or is simply a continuum of the classical 1p36 deletion phenotype.

  • Triplosensitivity score: 2
  • Strength of Evidence (disclaimer): Some evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

Though there have been several reports of duplications and triplications within 1p36, the phenotypes reported have been inconsistent. This is likely due to differences in duplication size and location within 1p36 between patients, as well as the presence or absence of other genomic imbalances. Interpretations of these duplications should be made in the context of the individual clinical presentation and the specific gene(s) involved. As evidence regarding the triplosensitivity of this region is emerging, the triplosensitivity score for this region is currently a 2.