title: Two rare deletions upstream of the NRXN1 gene (2p16.3) affecting the non-coding mRNA AK127244 segregate with diverse psychopathological phenotypes in a family.
abstract: CNVs spanning the 2p16.3 (NRXN1) and the 15q11.2 gene rich region have been associated with severe neuropsychiatric disorders including schizophrenia. Recently, studies have also revealed that CNVs in non-coding regions play an essential role in genomic variability in addition to disease susceptibility. In this study, we describe a family affected by a wide range of psychiatric disorders including early onset schizophrenia, schizophreniform disorder, and affective disorders. Microarray analysis identified two rare deletions immediately upstream of the NRXN1 gene affecting the non-coding mRNA AK127244 in addition to the pathogenic 15q11.2 deletion in distinct family members. The two deletions upstream of the NRXN1 gene were found to segregate with psychiatric disorders in the family and further similar deletions have been observed in patients diagnosed with autism spectrum disorder. Thus, we suggest that non-coding regions upstream of the NRXN1 gene affecting AK127244 might (as NRXN1) contain susceptibility regions for a wide spectrum of neuropsychiatric disorders.
authors.affiliation: Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark.
authors.forename: Linh T T
authors.initials: LT
authors.lastname: Duong
authors.affiliation: Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark. Electronic address: Louise.k.enggaard.hoeffding@regionh.dk.
authors.forename: Louise K
authors.initials: LK
authors.lastname: Hoeffding
authors.affiliation: The Child and Adolescent Psychiatry of Southern Denmark, Kolding, Denmark.
authors.forename: Kirsten B
authors.initials: KB
authors.lastname: Petersen
authors.affiliation: The Child and Adolescent Psychiatry of Southern Denmark, Kolding, Denmark.
authors.forename: Charlotte D
authors.initials: CD
authors.lastname: Knudsen
authors.affiliation: Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark.
authors.forename: Johan H
authors.initials: JH
authors.lastname: Thygesen
authors.affiliation: Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Klitten
authors.affiliation: Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Tommerup
authors.affiliation: deCODE Genetics, Reykjavik, Iceland.
authors.forename: Andrés
authors.initials: A
authors.lastname: Ingason
authors.affiliation: Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark; Department of Clinical Medicine, University of Copenhagen, DK-2200, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Werge
mesh_terms: D024506:5' Flanking Region; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2; D019295:Computational Biology / Q000379:methods; D004252:DNA Mutational Analysis; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D001523:Mental Disorders / Q000175:diagnosis* / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules; D010375:Pedigree; D010641:Phenotype; D062085:RNA, Long Noncoding / Q000235:genetics*; D017384:Sequence Deletion
chemical_list: C000611406:AK127244 long non-coding RNA, human; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; C539628:NRXN1 protein, human; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; D062085:RNA, Long Noncoding
keywords: 15q11.2 deletion; 2p16.3 (NRXN1) deletion; AK127244; Deletions; Family study; Non-coding regions; Schizophrenia