Details

Autor(en) / Beteiligte

• Kim, Hyung-Goo
• Kishikawa, Shotaro
• Higgins, Anne W.
• Seong, Ihn-Sik
• Donovan, Diana J.
• Shen, Yiping
• Lally, Eric
• Weiss, Lauren A.
• Najm, Juliane
• Kutsche, Kerstin
• Descartes, Maria
• Holt, Lynn
• Braddock, Stephen
• Troxell, Robin
• Kaplan, Lee
• Volkmar, Fred
• Klin, Ami
• Tsatsanis, Katherine
• Harris, David J.
• Noens, Ilse
• Pauls, David L.
• Daly, Mark J.
• MacDonald, Marcy E.
• Morton, Cynthia C.
• Quade, Bradley J.
• Gusella, James F.

Titel

Disruption of Neurexin 1 Associated with Autism Spectrum Disorder

Ist Teil von

• American journal of human genetics, 2008-01, Vol.82 (1), p.199-207

Ort / Verlag

Chicago, IL: Elsevier Inc

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 α- 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 ∼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 α-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.