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
18726931 2009 review of all currently described FOXL2 mutations in blepharophimosis/ptosis/epicanthus inversus syndrome (BPES) and premature ovarian failure. Overall, genomic rearrangements account for 19% (n = 145) of all molecular defects found in BPES.
15962237 Report of 5 deletions outside of the FOXL2 gene in probands with BPES phenotype indistinguishable from intragenic mutations. Study also characterizes 9 novel whole or partial FOXL2 deletions
20232352 Report of one known and 16 novel FOXL2 encompassing deletions in a cohort of BPES patients, some of which have associated clinical phenotypes, presumably related to the loss or disruption of genes proximal to FOXL2.

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.