ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000011.9) (NC_000011.10)
Evidence for haploinsufficiency phenotype
PubMed ID Description
15372379 Niemitz (2004): Authors describe a patient with Beckwith-Wiedemann syndrome with a maternally-inherited 250 kb deletion of KCNQ10T1. Reduced expression of CDKN1C was shown.
  • Triplosensitivity score: 2
  • Strength of Evidence (disclaimer): Some evidence for dosage pathogenicity
Evidence for triplosensitivity phenotype
PubMed ID Description
21920939 Chiesa (2012): Authors report a patient with Beckwith-Wiedemann syndrome with a maternally-inherited 160 kb duplication involving the imprinting control region 2 (the promoter of KCNQ10T1 - Smilinich, et al. PMID: 10393948), a portion of KCNQ1, and most of 5' KCNQ10T1. The imprinting control region 2 was hypomethylated and CDKN1C expression was reduced.
21780245 Demars (2011): Authors report a case of familial Beckwith-Wiedemann syndrome with a maternally-inherited 50 kb duplication involving two CpG islands in the imprinting control region 2, resulting in decreased CDKN1C expression and increased KCNQ10T1 expression.

Triplosensitivity phenotype comment:

The duplications described in Chiesa (2012) and Demars (2011) lead to aberrant methylation and decreased CDKN1C expression leading to BWS. However, it is not clear that all duplications of this gene would be functionally similar. Therefore, methylation testing of the ICR2 region and inheritance patterns would be necessary to establish a functional link between a duplication and the BWS phenotype.