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
15551338 A 15-month-old boy was described with a de novo interstitial inverted duplication of 3q24-q26.31. Clinical evaluation revealed mild but typical features of dup(3q) syndrome. The duplication was characterized by conventional and molecular cytogenetics. The results of fluorescence in situ hybridization (FISH) analysis with BAC probes suggested a disruption of the NLGN1 gene at the distal end of the duplication in 3q26.31 in the patient. The breakpoint within NLGN1 was apparently unique for this patient, and the contribution of NLGN1 disruption to the phenotype of this patient remained unclear.
22106001 A 2.2?Mb deletion at 3q26.3-3q26.32-encompassing the terminal end of NLGN1 and the entire NAALADL2 gene-detected by genomic microarray, and confirmed by FISH and real-time quantitative PCR. The same size deletion was subsequently found in her healthy, asymptomatic, adult mother. In Coe et al., 2014 (PMID: 25217958), NLGN1 deletions were detected in a few patients but not in controls; however, due to the rarity, it was not possible to show significance.

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.