ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000014.8) (NC_000014.9)
  • Haploinsufficiency score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Haploinsufficiency phenotype comments:

PMID:15505031: Aijaz et al. (2004) analyzed 173 individuals with anophthalmia, microphthalmia, or coloboma for SIX6 mutations. They found 6 mutations, which were all also present in the 131 controls tested. PMID:15266624: Gallardo et al. (2004) analyzed 73 patients with anophthalmia/microphthalmia for mutations in SIX6. They found 4 mutations and 3 of these were present in normal controls. The fourth mutation was a thr165-to-ala missense mutation in exon 1 that was inherited from a normal father, but not found in 80 normal controls. No functional studies were performed on this missense change.

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

Triplosensitivity phenotype comment:

PMID:18666230: Ou et al. (2008) report a patient with DD and MCA, including features suggestive of either branchiootorenal syndrome (BOR) or oculoauriculovertebral spectrum (OAVS). CMA revealed an ~12 Mb duplication of 14q22.3-q23.3 and a loss of ~4 Mb sequence in 13q21.31-q21.32 in the proband and his abnormal father (ID, short stature, hypernasal speech, and minor craniofacial anomalies). The authors suggest that the "increased dosage of SIX1, SIX6, or OTX2 may be responsible for the BOR and OAVS-like features in this family." The duplication of chr14 contains a total of 51 genes.