title: Beta-catenin in schizophrenia: Possibly deleterious novel mutation.
abstract: Schizophrenia is a debilitating psychiatric disorder, affecting approximately 1% of the human population. Mostly genetic factors contribute to schizophrenia, but the genetics are complex and various aspects of brain functioning and structure, from development to synapse plasticity, seem to be involved in the pathogenesis. The goal of the study was to look for novel mutations in genes, implicated in molecular networks, important in schizophrenia. In the study four candidate genes taking part in the WNT signaling pathway were analyzed by sequencing in a cohort of 87 schizophrenia patients from Saint Petersburg, Russia. The gene list included CTNNB1 (beta-catenin), GSK3B, WNT2B and WNT7B. The impact of discovered variants on the protein function was analyzed in silico. We found three variants in the genes CTNNB1 and WNT7B, absent in healthy controls, including 212 controls from the same geographic area. The novel mutation c.1943A>G (p.N648S) in CTNNB1 seems to be the best candidate for disease-associated mutation in this study, as it damages the protein product in silico. This is the first study reporting mutations in CTNNB1 in schizophrenia.
authors.affiliation: Faculty of Biology, Saint Petersburg State University, Saint Petersburg, Russia. Electronic address: anastasia.levchenko@mail.mcgill.ca.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Levchenko
authors.affiliation: Department of Psychiatry and Addiction Medicine, Faculty of Medicine, Saint Petersburg State University, Saint Petersburg, Russia.
authors.forename: Stepan
authors.initials: S
authors.lastname: Davtian
authors.affiliation: Institute of Molecular Biology and Genetics, Federal Almazov Medical Research Center, Saint Petersburg, Russia.
authors.forename: Olga
authors.initials: O
authors.lastname: Freylichman
authors.affiliation: Faculty of Biology, Saint Petersburg State University, Saint Petersburg, Russia.
authors.forename: Maria
authors.initials: M
authors.lastname: Zagrivnaya
authors.affiliation: Institute of Molecular Biology and Genetics, Federal Almazov Medical Research Center, Saint Petersburg, Russia; ITMO University, Institute of Translational Medicine, Saint Petersburg, Russia.
authors.forename: Anna
authors.initials: A
authors.lastname: Kostareva
authors.affiliation: Faculty of Biology, Saint Petersburg State University, Saint Petersburg, Russia; Institute of Experimental Medicine, Northwestern Branch of the Russian Academy of Medical Sciences, Saint Petersburg, Russia. Electronic address: y.malashichev@spbu.ru.
authors.forename: Yegor
authors.initials: Y
authors.lastname: Malashichev
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D056726:Genetic Association Studies; D014644:Genetic Variation / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D012426:Russia; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D012565:Schizophrenic Psychology; D051153:Wnt Proteins / Q000235:genetics; D055815:Young Adult; D051176:beta Catenin / Q000235:genetics*
chemical_list: D006023:Glycoproteins; C115496:WNT2B protein, human; D051153:Wnt Proteins; D051176:beta Catenin
keywords: Candidate gene analysis; DNA mutational analysis; Human protein CTNNB1; Psychiatry