ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000002.11) (NC_000002.12)
Evidence for haploinsufficiency phenotype
PubMed ID Description
14581620 Roessler et al. describe a W113X mutation found in siblings. Mutation not identified in either parent, suggesting gonadal mosaicism. Surviving sibling with bilateral cleft lip and palate, microcephaly; single central incisor; postaxial polydactyly; growth hormone deficiency. Deceased sibling with single nostril; hypoplastic palate; alobar HPE; absent lobe of the pituitary. Not found in >200 normal control chromosomes.
21204792 Bertolacini et al. report 2 patients with frameshift/nonsense mutations. The first, p. Ser51fsX536, was described in a woman with midline facial dysmorphic features, postaxial polydactyly, and a normal MRI; the same change was also found in her mother with hypotelorism. The second, p. P288fsX301, was found in a patient with semilobar HPE, midline dysmorphic facial features, and postaxial polydactyly; the same change was also found in the patient's mother, who had postaxial polydactyly.
20685856 Franca et al. report 3 novel, heterozygous frameshift/nonsense mutations found in individuals without abnormal MRI findings but with pituitary hormone deficiency, variable polydactyly, and midline facial defects. In family 1, p. L788fsX794 was identified in 12 individuals over 4 generations with polydactyly and hypopituitarism. The change was not found in unaffected family members. In family 2, p. L694fsX722 was identified in an individual with severe growth retardation, cleft lip/palate, and a flat nasal bridge. Another variant in GLI2 was also found in this individual and his father, but was not found in 155 healthy controls. In family 3, p. E380X was found in an individual with developmental delay, hypothyroidism, and hypocortisolism. The mutation was found in her reportedly normal mother, but not in 204 alleles from normal individuals.

Haploinsufficiency phenotype comments:

There are known issues of variable expressivity and reduced penetrence associated with this phenotype.

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