ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function 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.

Evidence for Triplosenstive Phenotype

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.

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.