ClinGen Dosage Sensitivity Curation Page


Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
16826528 Kleefstra et al. (2006): Describes mutations in EHMT1 in individuals with features characteristic of the 9q telomere microdeletion syndrome (Kleefstra syndrome), including one de novo nonsense mutation and one de novo frameshift predicted to result in protein truncation.
19264732 Kleefstra et al. (2009): Additional changes in EHMT1 are described in individuals exhibiting features of the 9q telomere microdeletion syndrome, including a deletion only involving EHMT1, two additional nonsense mutations, and an additional frameshift mutation predicted to result in protein truncation.

Evidence for Triplosenstive Phenotype

Evidence for triplosensitivity phenotype
PubMed ID Description
22083728 Kirov et al. (2007): A de novo duplication involving only EHMT1 was reported in a study of individuals with schizophrenia. Little other clinical information was available, though the patient was noted to be developmentally normal and to be overweight.

NOTE:The loss of function score should be used to evaluate deletions, and the triplosensitivity score should be used to evaluated duplications. CNVs encompassing more than one gene must be evaluated in their totality (e.g. overall size, gain vs. loss, presence of other genes, etc). The rating of a single gene within the CNV should not necessarily be the only criteria by which one defines a clinical interpretation. Individual interpretations must take into account the phenotype described for the patient as well as issues of penetrance and expressivity of the disorder. ACMG has published guidelines for the characterization of postnatal CNVs, and these recommendations should be utilized (Genet Med (2011)13: 680-685). Exceptions to these interpretive correlations will occur, and clinical judgment should always be exercised.