ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000001.10) (NC_000001.11)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

There have been several families with ocular abnormalities including anterior segment mesenchymal dysgenesis, cataracts, and/or microphthalmia with mutations identified in FOXE3, both autosomal dominant and recessive. Almost all of the autosomal dominant families have had heterozygous mutations that result in the addition of amino acids to the C-terminus due to either a frameshift or non-stop (abolished stop codon) mutations (PMIDs:11159941, 21150893, 19708017, 20806047). Doucette et al (2011, PMID:21150893) sequenced cDNA from lymphoblasts and did not detect any evidence of the mutation, suggesting that either the mutant mRNA was degraded or not transcribed. However, FOXE3 is normally only expressed in lens epithelium. No other functional studies have been done. Homozygous mutations identified in the recessive families include nonsense and frameshift mutations and carrier parents are unaffected (PMID:24033328, 22204637, 20664696, 20361012, 20140963, 16826526). Considering the lack of a phenotype in heterozygotes in these families, and the unique nature of the mutations in the dominant families, haploinsufficiency seems an unlikely mechanism for these dominant ocular phenotypes. However, further function studies of the mutations in the dominant families are needed.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity