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
11078474 Fang et al. 2000: Describe a nonsense mutation and a frameshift mutation predicted to result in premature truncation in two unrelated families with lymphedema-distichiasis (LD) syndrome. The phenotype was variable amongst all affected family members. Two carrier individuals in family 1 (with the nonsense mutation) were fetuses electively terminated due to hydrops fetalis. The proband of the second family (frameshift mutation) was found to have the "additional features of cystic hygroma, arachnoid cysts, and cleft palate." The authors proposed that their features were due to haploinsufficiency of FOXC2, though no functional studies were performed.
11694548 Erickson et al. 2001: Describe 5 additional families with LD syndrome and mutations in FOXC2, including two novel nonsense mutations.
21918810 de Bruyn et al. 2012: A nonsense mutation was identified in a newborn girl who had hydrops and severe pulmonary lymphangiectasia. This was inherited from her father who had distichiasis and adult-onset lymphedema.

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.