ClinGen Dosage Sensitivity Curation Page

1q21.1 recurrent region (BP3-BP4, distal) (includes GJA5)

  • Curation Status: Complete
  • id: ISCA-37421
  • Date last evaluated: 2016-04-14
  • Issue Type: ClinGen Region Curation
  • ClinGen Haploinsufficiency Score: 3
  • ClinGen Triplosensitivity Score: 3


Location Information

  • 1q21.1-q21.2
  • GRCh37/hg19 chr1: 146,577,486-147,394,506
  • View: NCBI | Ensembl | UCSC
  • GRCh38/hg38 chr1: 147,105,904-147,917,509
  • View: NCBI | Ensembl | UCSC
Select assembly: (NC_000001.10) ()
Evidence for haploinsufficiency phenotype
PubMed ID Description
http://www.ncbi.nlm.nih.gov/books/NBK52787/

Haploinsufficiency phenotype comments:

This region is also known as the distal 1q21.1 (BP3-BP4-flanked region). Both incomplete penetrance and variable expressivity have been demonstrated for deletion of the distal 1q21.1 region. Note that genes used as landmarks are not necessarily causative of the complete phenotype(s) associated with the region.

Evidence for triplosensitivity phenotype
PubMed ID Description
3298277 From a cohort of 948 patients with tetralogy of Fallot (TOF), 1488 patients with other forms of congenital heart disease (CHD) and 6740 ethnically matched controls Soemedi et al (2011) found that the 1q21.1 duplication was more common in cases of TOF than in controls p value = 2.2E-7, but the deletion was not. They also detected 3 small duplications (100-200 kb) that encompassed a single gene in common, GJA5. The small duplication was enriched in cases of TOF in comparison to controls (p value = 0.01) suggesting GJA5 as the gene responsible for the CHD phenotype.
3817079 Dolcetti et al. (2013) comprehensively reviewed all reports of 1q21.1 duplications to date, focusing on expression of clinical features in the adult population. In total 107 individuals from 76 families were identified from the literature reviewed and seven adult cases were reported from studies of schizophrenia and tetralogy of Fallot (TOF) at their center. Their study showed that 1q21.1 duplication is significantly enriched in populations of patients with major developmental conditions, including TOF and schizophrenia.
http://www.ncbi.nlm.nih.gov/books/NBK52787/

Triplosensitivity phenotype comment:

This region is also known as the distal 1q21.1 (BP3-BP4-flanked region). Both incomplete penetrance and variable expressivity have been demonstrated for duplication of the distal 1q21.1 region. Note that genes used as landmarks are not necessarily causative of the complete phenotype(s) associated with the region.