ClinGen Dosage Sensitivity Curation Page

7q11.23 recurrent (Williams-Beuren syndrome) region (includes ELN)

  • Curation Status: Complete
  • id: ISCA-37392
  • Date last evaluated: 2015-08-06
  • Issue Type: ClinGen Region Curation
  • ClinGen Haploinsufficiency Score: 3
  • ClinGen Triplosensitivity Score: 3


Location Information

Select assembly: (NC_000007.13) ()

Haploinsufficiency phenotype comments:

Deletion of this region is associated with Williams-Beuren syndrome (WBS, synonym: Williams syndrome). Clinical findings in WBS may include: cardiovascular abnormalities, craniofacial anomalies, connective tissue abnormalities, intellectual disability, urogenital anomalies, dysmorphic features, and unique personality traits. WBS shows complete penetrance and variable expressivity. The majority of WBS cases are de novo. Note that genes used as landmarks are not necessarily causative of the complete phenotype(s) associated with the region.

Triplosensitivity phenotype comment:

Duplication of this region is associated with Duplication 7q11.23 syndrome. With 48 patients currently reported in the literature (see PMIDs 26109321, 22369319, 19249392, 17666889), there is sufficient evidence to support the triplosensitivity of this region. Clinical findings in Duplication 7q11.23 syndrome may include: speech delay, autistic features (PMID: 21658581), motor delay, seizures, hypotonia, brain anomalies, joint laxity, and craniofacial abnormalities. Duplication 7q11.23 syndrome is considered to be highly penetrant with patients showing variable expressivity. In a large-scale case-control comparison study of the relative prevalence of copy number variants in children with ID/DD, MCA, and other developmental phenotypes compared to controls, 7q11.23 duplications were observed in 28/29,085 cases versus 0/19,584 controls (p=5.46E-7) Coe et al. 2014; PMID 25217958; see also Cooper et al. 2011; PMID 25424174). Both inherited and de novo cases of 7q11.23 duplications have been reported in the literature. Note that genes used as landmarks are not necessarily causative of the complete phenotype(s) associated with the region.