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Intragenic rearrangements in NRXN1 in three families with autism spectrum disorder, developmental delay, and speech delay


  • The identified rearrangements have been deposited in GenBank: NRXN1_intragenic_deletion FJ972627; NRXN1_intragenic_duplication1 FJ972628; NRXN1_intragenic_duplication2 FJ972629.

  • How to cite this article: Wiśniowiecka-Kowalnik B, Nesteruk M, Peters SU, Xia Z, Cooper ML, Savage S, Amato RS, Bader P, Browning MF, Haun CL, Duda AW III, Cheung SW, Stankiewicz P. 2010. Intragenic Rearrangements in NRXN1 in Three Families With Autism Spectrum Disorder, Developmental Delay, and Speech Delay. Am J Med Genet Part B 153B:983–993.


NRXN1 is highly expressed in brain and has been shown recently to be associated with ASD, schizophrenia, cognitive and behavioral abnormalities, and alcohol and nicotine dependence. We present three families, in whom we identified intragenic rearrangements within NRXN1 using a clinical targeted oligonucleotide array CGH. An ∼380 kb deletion was identified in a woman with Asperger syndrome, anxiety, and depression and in all four of her children affected with autism, anxiety, developmental delay, and speech delay but not in an unaffected child. An ∼180 kb tandem duplication was found in a patient with autistic disorder and cognitive delays, and in his mother and younger brother who have speech delay. An ∼330 kb tandem duplication was identified in a patient with autistic features. As predicted by conceptual translation, all three genomic rearrangements led to the premature truncation of NRXN1. Our data support previous observations that NRXN1 may be pathogenic in a wide variety of psychiatric diseases, including autism spectrum disorder, global developmental delay, anxiety, and depression. © 2010 Wiley-Liss, Inc.