De novo mutations in the gene encoding the synaptic scaffolding proteinSHANK3in patients ascertained for schizophrenia

• DOI: 10.1073/pnas.0906232107
• Publication Date: 2010-04-13T03:45:08Z
• Authors: Julie Gauthier; Nathalie Champagne; Ronald G. Lafrenière; Lan Xiong; Dan Spiegelman; Edna Brustein; Mathieu Lapointe; Huashan Peng; Mélanie Côté; Anne Noreau; Fadi F. Hamdan; Anjené M. Addington; Judith L. Rapoport; Lynn E. DeLisi; Marie-Odile Krebs; Ridha Joober; Ferid Fathalli; Fayçal Mouaffak; Ali P. Haghighi; Christian Néri; Marie-Pierre Dubé; Mark E. Samuels; Claude Marineau; Eric A. Stone; Philip Awadalla; Philip A. Barker; Salvatore Carbonetto; Pierre Drapeau; Guy A. Rouleau; ; Kathleen Daignault; Ousmane Diallo; Joannie Duguay; Marina Drits; Edouard Henrion; Philippe Jolivet; Frédéric Kuku; Karine Lachapelle; Guy Laliberté; Sandra Laurent; Meijiang Liao; Carlos Marino; Amélie Piton; Annie Raymond; Annie Reynolds; Daniel Rochefort; Judith St-Onge; Pascale Thibodeau; Kazuya Tsurudome; Yan Yang; Sophie Leroy; Katia Ossian; Mélanie Chayet; David Gourion
• Keywords: Male; Neurons; 0303 health sciences; Base Sequence; Molecular Sequence Data; Mutation, Missense; Computational Biology; Nerve Tissue Proteins; Sequence Analysis, DNA; Pedigree; Rats; 3. Good health; 03 medical and health sciences; Schizophrenia; Animals; Humans; Female; Amino Acid Sequence; Carrier Proteins; Zebrafish; DNA Primers; Microsatellite Repeats

Schizophrenia likely results from poorly understood genetic and environmental factors. We studied the gene encoding synaptic protein SHANK3 in 285 controls 185 schizophrenia patients with unaffected parents. Two de novo mutations (R1117X R536W) were identified two families, one being found three affected brothers, suggesting germline mosaicism. Zebrafish rat hippocampal neuron assays revealed behavior differentiation defects resulting R1117X mutant. As previously reported autism, occurrence of subjects a phenotype suggests molecular link between these neurodevelopmental disorders.