title: Intragenic rearrangements in NRXN1 in three families with autism spectrum disorder, developmental delay, and speech delay.
abstract: 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 approximately 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 approximately 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 approximately 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.
authors.affiliation: Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Wiśniowiecka-Kowalnik
authors.forename: Monika
authors.initials: M
authors.lastname: Nesteruk
authors.forename: Sarika U
authors.initials: SU
authors.lastname: Peters
authors.forename: Zhilian
authors.initials: Z
authors.lastname: Xia
authors.forename: M Lance
authors.initials: ML
authors.lastname: Cooper
authors.forename: Sarah
authors.initials: S
authors.lastname: Savage
authors.forename: R Stephen
authors.initials: RS
authors.lastname: Amato
authors.forename: Patricia
authors.initials: P
authors.lastname: Bader
authors.forename: Marsha F
authors.initials: MF
authors.lastname: Browning
authors.forename: Christa L
authors.initials: CL
authors.lastname: Haun
authors.forename: Andrew Walter
authors.initials: AW
authors.lastname: Duda
authors.forename: Sau Wai
authors.initials: SW
authors.lastname: Cheung
authors.forename: Paweł
authors.initials: P
authors.lastname: Stankiewicz
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000235:genetics*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000150:complications* / Q000235:genetics*; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D002658:Developmental Disabilities / Q000150:complications* / Q000235:genetics*; D005190:Family; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D007805:Language Development Disorders / Q000150:complications* / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D017422:Sequence Analysis, DNA
chemical_list: D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; C539628:NRXN1 protein, human; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules