title: Mutations of the Nogo-66 receptor (RTN4R) gene in schizophrenia.
abstract: Schizophrenia (SCZD) or schizoaffective disorders are quite common features in patients with DiGeorge/velo-cardio-facial syndrome (DGS/VCFS) as a result of chromosome 22q11.2 aploinsufficiency. We evaluated the Nogo-66 receptor gene (RTN4R), which maps within the DGS/VCFS critical region, as a potential candidate for schizophrenia susceptibility. RTN4R encodes for a functional cell surface receptor, a glycosylphosphatidylinositol (GPI)-linked protein, with multiple leucine-rich repeats (LRR), which is implicated in axonal growth inhibition. One hundred and twenty unrelated Italian schizophrenic patients were screened for mutations in the RTN4R gene using denaturing high performance liquid chromatography (DHPLC). Three mutant alleles were detected, including two missense changes (c.355C>T; R119W and c.587G>A; R196H), and one synonymous codon variant (c.54G>A; L18L). The two schizophrenic patients with the missense changes were strongly resistant to the neuroleptic treatment at any dosage. Both missense changes were absent in 300 control subjects. Molecular modeling revealed that both changes lead to putative structural alterations of the native protein.
authors.affiliation: IRCCS-C.S.S. San Giovanni Rotondo, 00198 Rome, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Sinibaldi
authors.forename: Alessandro
authors.initials: A
authors.lastname: De Luca
authors.forename: Emanuele
authors.initials: E
authors.lastname: Bellacchio
authors.forename: Emanuela
authors.initials: E
authors.lastname: Conti
authors.forename: Augusto
authors.initials: A
authors.lastname: Pasini
authors.forename: Claudio
authors.initials: C
authors.lastname: Paloscia
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Spalletta
authors.forename: Carlo
authors.initials: C
authors.lastname: Caltagirone
authors.forename: Antonio
authors.initials: A
authors.lastname: Pizzuti
authors.forename: Bruno
authors.initials: B
authors.lastname: Dallapiccola
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid; D003062:Codon / Q000235:genetics; D004252:DNA Mutational Analysis; D004062:DiGeorge Syndrome / Q000235:genetics; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D009154:Mutation; D020125:Mutation, Missense; D009185:Myelin Proteins / Q000737:chemistry / Q000235:genetics*; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D003062:Codon; D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070816:Nogo Receptor 1; C486580:RTN4R protein, human; D011956:Receptors, Cell Surface