Maintenance has been completed and SciCrunch services have been restored. We apologize for any inconvenience it may have caused.

Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Disruption of neurexin 1 associated with autism spectrum disorder.

Autism is a neurodevelopmental disorder of complex etiology in which genetic factors play a major role. We have implicated the neurexin 1 (NRXN1) gene in two independent subjects who display an autism spectrum disorder (ASD) in association with a balanced chromosomal abnormality involving 2p16.3. In the first, with karyotype 46,XX,ins(16;2)(q22.1;p16.1p16.3)pat, NRXN1 is directly disrupted within intron 5. Importantly, the father possesses the same chromosomal abnormality in the absence of ASD, indicating that the interruption of alpha-NRXN1 is not fully penetrant and must interact with other factors to produce ASD. The breakpoint in the second subject, with 46,XY,t(1;2)(q31.3;p16.3)dn, occurs approximately 750 kb 5' to NRXN1 within a 2.6 Mb genomic segment that harbors no currently annotated genes. A scan of the NRXN1 coding sequence in a cohort of ASD subjects, relative to non-ASD controls, revealed that amino acid alterations in neurexin 1 are not present at high frequency in ASD. However, a number of rare sequence variants in the coding region, including two missense changes in conserved residues of the alpha-neurexin 1 leader sequence and of an epidermal growth factor (EGF)-like domain, respectively, suggest that even subtle changes in NRXN1 might contribute to susceptibility to ASD.

Pubmed ID: 18179900

Authors

  • Kim HG
  • Kishikawa S
  • Higgins AW
  • Seong IS
  • Donovan DJ
  • Shen Y
  • Lally E
  • Weiss LA
  • Najm J
  • Kutsche K
  • Descartes M
  • Holt L
  • Braddock S
  • Troxell R
  • Kaplan L
  • Volkmar F
  • Klin A
  • Tsatsanis K
  • Harris DJ
  • Noens I
  • Pauls DL
  • Daly MJ
  • MacDonald ME
  • Morton CC
  • Quade BJ
  • Gusella JF

Journal

American journal of human genetics

Publication Data

January 8, 2008

Associated Grants

  • Agency: NIMH NIH HHS, Id: MH64547
  • Agency: NIGMS NIH HHS, Id: P01 GM061354
  • Agency: NIGMS NIH HHS, Id: P01-GM061354
  • Agency: NICHD NIH HHS, Id: P01-HD00300838
  • Agency: NINDS NIH HHS, Id: R01-NS16648
  • Agency: NICHD NIH HHS, Id: U19-HD35482

Mesh Terms

  • Autistic Disorder
  • Chromosome Aberrations
  • Chromosomes, Human, Pair 2
  • Genetic Predisposition to Disease
  • Glycoproteins
  • Humans
  • Mutation, Missense
  • Neuropeptides
  • Protein Structure, Tertiary
  • Sequence Analysis, DNA