ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000012.11) (NC_000012.12)
Evidence for haploinsufficiency phenotype
PubMed ID Description
15489854 Hellemans et al. (2004): Describes loss-of-function mutations identified in three families with variable expressivity for osteopoikilosis, Buschke-Ollendorf syndrome, and melorheostosis, as well as in three unrelated individuals with osteopoikilosis. Two nonsene mutations were reported, along with three frameshift mutations and one splice-site with frameshift were reported; all were believed to result in loss-of-function. Of note, the paper also reports a case of an individual with osteopoikilosis, microcephaly, ectopic kidneys, and learning disabilities who was found to have a microdeletion enccompassing LEMD3 as well as a number of other genes.
17087626 Mumm et al. (2007): Describes 4 additional mutations, including one nonsense mutation (L478X) in family with osteopoikilosis, another nonsense mutation (R655X) in a family with osteopoikilosis and melorheostosis, and another nonsense (Y441X) mutation in a family with Buschke-Ollendorf syndrome.
19438932 Zhang et al. (2009): Describes a W855X mutation described in a boy with Buschke-Ollendorf syndrome and his father with osteopoikilosis.

Haploinsufficiency phenotype comments:

Loss-of-function mutations in LEMD3 are associated with osteopoikilosis, Buschke-Ollendorf syndrome, and melorheostosis. Variable expressivity has been reported, with members of the same family exhibiting each of these different phenotypes. Mutations in LEMD3 have not been observed in individuals with isolated meloreostosis.

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