ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000017.10) (NC_000017.11)
Evidence for haploinsufficiency phenotype
PubMed ID Description
22305528 Lines et al (2012) reported 12 patients with mandibulofacial dysostosis and microcephaly (MFDM) who had heterozygous, de novo mutations identified via exome sequencing. The mutations included 2 deletions, 3 nonsense, 1 splice-site, 3 frameshift, and 3 missense.
23188108 Gordon et al (2012) report 10 patients with features consistent with MFDM, some of whom also had esophageal atresia. Some of these patients had received an initial diagnosis of Feingold syndrome, CHARGE, VATER, or OAVS. Heterozygous de novo mutations, including 1 nonsense, 1 frameshift, and 3 splicing mutations, were found in 5 individuals. One pre-term affected baby had a splice mutation that was inherited from a mother thought to have Feingold syndrome. The remaining patients either had deletions found by microarray that contained EFTUD2 and other genes or had mutations with unknown inheritance.

Haploinsufficiency phenotype comments:

Heterozygous loss of function mutations have recently been shown to cause mandibulofacial dysostosis and microcephaly. Phenotypic variability has been shown that overlaps several other syndromes. In addition to the two papers above, other reports of mutations include Bernier et al (2012, PMID:22541558) and Luquetti et al (2013, PMID:23239648).

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