ClinGen Dosage Sensitivity Curation Page

ARCN1

Curation Status: Complete

Gene Information

Location Information

Evidence for Loss Phenotypes

Evidence for loss of function phenotype
PubMed ID Description
27476655 Izumi et al [2016] describe 4 unrelated individuals with heterozygous loss of function mutations in ARCN1 resulting in facial dysmorphisms, including severe micrognathia, rhizomelic shortening, and microcephalic dwarfism. The mutations included 2 missense, one nonsense, and one frameshift. Functional studies confirmed reduced mRNA expression, and Western blot demonstrated reduced protein expression.

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.