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
21131976 Dauwerse et al. (2011) describe 17 mutations in POLR1D detected in 20 unrelated individuals with clinical diagnoses of Treacher-Collins syndrome and no mutations in TCOF1, including 10 different nonsense mutations. This group also describes a 156 kb de novo deletion encompassing all of POLR1D and the first exon of LNX2. The mutations segregated with disease in familial cases. Two families demonstrated reduced penetrance.

Evidence for Triplosenstive Phenotype

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.