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
8012388 Nicholson et al. (1994) found a 2 bp deletion in PMP22 (207TC) that resulted in a frameshift was found in all affected family members with HNPP.
9040737 Young et al. (1997) found a 1 bp insertion in PMP22 (325G) that resulted in a frameshift and inclusion of an additional 127 amino acids in family members affected with HNPP but not in normal family members.
9712007 Lenssen et al. (1998) report on six HNPP families with an insertion resulting in a frameshift (Gly94fs). They compared the phenotypes of these families compared to families with the common 1.5 Mb deletion and found that the frameshift mutation resulted in HNPP with additional neuropathy features similar to CMT1.

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.