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
15338008 2004 study of 7 individuals with Dandy-Walker malformation (DWM) and heterozygous 3q2 deletions defined a critical DWM region encompassing ZIC1 and ZIC4 and demonstrated a similar phenotype in double heterozygous knockout mice.
21204220 2011 report of a patient with DWM and heterozygous ZIC1 and ZIC4 deletion. Deletion was found by chromosome analysis extended 14 Mb and involved many other genes.

Evidence for Triplosenstive Phenotype

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.