ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000002.11) (NC_000002.12)
  • Haploinsufficiency score: 3
  • Strength of Evidence (disclaimer): Sufficient evidence for dosage pathogenicity
Evidence for haploinsufficiency 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.

Haploinsufficiency phenotype comments:

Heterozygous deletions of NRXN1 have been reported in individuals with autism, schizophrenia, and ID. Other PMIDs including: 21424692; 19557195, 18369103 describe both case reports and case-control studies supporting a role for the haploinsufficiency of NRXN1 in neurological phenotypes. Compound heterozygosity reported in one individual with Pitt-Hopkins-like syndrome 2-severe ID, autistic behavior, dysmorphism.(PMID 19896112) Several intronic deletion polymorphisms, particularly in the longer isoform, have been reported in NRXN1 and are cataloged in DGV

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity