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
20162629 Wisniomiecka-Kowalnik et al. (2010) identified three families with NRXN1 rearrangements and autism spectrum disorder. A 380-kb deletion was identified in a woman with Asperger syndrome and in four of her children affected with autism, DD, and speech delay, but not in her unaffected child.
18057082 Zahir et al (2008) describe a de novo 321 kb deletion including only NRXN1 (exons 1-5 of a-form) in a child with DD, autism, unusual facies. Note: This is the same individual described in PMID:16909388 -Friedman et al (2006)
20468056 Ching et al (2010): 12 subjects of 3,540 referred for clinical aCGH were identified with exonic deletions of NRXN1. The phenotype of these individuals was variable and included autism, ID, language delays, and hypotonia. Comparing this cohort to a control population showed a statistically significant increase in NRXN1 deletion in cases versus controls (p=8.9x10(-7)). Further, two families were described with NRXN1 deletions (one exoninc, one of 5' regulatory region) that segregated with autism and ID in both families.

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.