title: Resequencing and follow-up of neurexin 1 (NRXN1) in schizophrenia patients.
abstract: Large rare deletions in NRXN1 increase the risk for schizophrenia. The aim of the present study was to determine whether small rare sequence changes in exons and splice sites contribute to the development of schizophrenia in a high-penetrance manner. Complete coding regions and splice sites were resequenced in 94 patients and 94 controls. Among the 16 rare sequence variants, two missense substitutions (E201G and I1068V) were observed in single patients but not in controls. Investigation of DNA samples from family members and in silico analysis of possible effects on protein function produced no evidence of high-penetrance genetic effects. Follow-up genotyping of the most promising findings (E201G and I1068V) in an independent sample of >1400 patients and >1100 controls revealed no overrepresentation in patients compared to controls (E201G: 0/1 and I1068V: 0/0). Since I1068V was observed in a single patient, it is impossible to exclude the possibility that I1068V makes a minor contribution to schizophrenia susceptibility. Overall, however, the results do not suggest the existence of rare, highly penetrant NRXN1 mutations in patients with schizophrenia.
authors.affiliation: Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany; Institute of Human Genetics, University of Bonn, Bonn, Germany.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Mühleisen
authors.forename: F Buket
authors.initials: FB
authors.lastname: Basmanav
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Forstner
authors.forename: Manuel
authors.initials: M
authors.lastname: Mattheisen
authors.forename: Lutz
authors.initials: L
authors.lastname: Priebe
authors.forename: Stefan
authors.initials: S
authors.lastname: Herms
authors.forename: Rene
authors.initials: R
authors.lastname: Breuer
authors.forename: Susanne
authors.initials: S
authors.lastname: Moebus
authors.forename: Igor
authors.initials: I
authors.lastname: Nenadic
authors.forename: Heinrich
authors.initials: H
authors.lastname: Sauer
authors.forename: Rainald
authors.initials: R
authors.lastname: Mössner
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Dan
authors.initials: D
authors.lastname: Rujescu
authors.forename: Michael
authors.initials: M
authors.lastname: Ludwig
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Markus M
authors.initials: MM
authors.lastname: Nöthen
authors.forename: Sven
authors.initials: S
authors.lastname: Cichon
mesh_terms: D000328:Adult; D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D005091:Exons / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D020125:Mutation, Missense / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019006:Neural Cell Adhesion Molecules; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology
chemical_list: D002135:Calcium-Binding Proteins; D015816:Cell Adhesion Molecules, Neuronal; C539628:NRXN1 protein, human; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules