Identification of SHANK2 Pathogenic Variants in a Chinese Uygur Population with Schizophrenia
- PDF / 609,596 Bytes
- 8 Pages / 595.276 x 790.866 pts Page_size
- 75 Downloads / 209 Views
Identification of SHANK2 Pathogenic Variants in a Chinese Uygur Population with Schizophrenia Han Zhang 1
&
Dong Wang 1 & Jianhua Chen 1,2 & Xiuli Li 1 & Qizhong Yi 3 & Yongyong Shi 1,2,3,4
Received: 1 March 2020 / Accepted: 19 May 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Genomic studies on schizophrenia (SCZ) have revealed several candidate genes involved in excitatory synapse function and plasticity associated with its etiology. SHANK2 is a postsynaptic scaffolding protein, which anchors a protein complex connecting NMDAR, AMPAR, and mGluR receptors at excitatory neuronal synapses. Mutations in the SHANK2 gene have been reported to be associated with human autism spectrum disorders (ASDs) and SCZ. To identify variants in the SHANK2 gene and determine the association of SHANK2 with SCZ in the Chinese Uygur population, we conducted targeted sequencing of whole exon regions and exon-intron boundaries of SHANK2 in 1574 SCZ patients and 1481 healthy controls. A total of 149 variants were identified, including six common variants and 143 rare variants. For common variants, rs62622853 and rs3924047 showed allelic significance with SCZ before correction, but the association was eliminated after Bonferroni correction. Seven rare nonsynonymous variants, p.Arg739Trp, p.Pro807Leu, p.Ile854Phe, p.Thr1322Ser, p.Leu1434Arg, p.Val1486Ile, and p.Thr1674Met, occurred only in the patients but not in any of the healthy controls. In silico analysis predicted that p.Arg739Trp, p.Leu1434Arg, and p.Val1486Ile variants are likely to be damaging. The present study suggests that individuals with two novel rare nonsynonymous variants (p.Arg739Trp, p.Leu1434Arg) and p.Val1486Ile variants of SHANK2 might increase the susceptibility to developing SCZ disorder. Keywords Schizophrenia . SHANK2 gene . Rare novel variant . Uygur Chinese
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s12031-020-01606-8) contains supplementary material, which is available to authorized users. * Qizhong Yi [email protected] * Yongyong Shi [email protected] 1
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University, Shanghai, China
2
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China
3
Psychological Medicine Center, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China
4
Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University, Affiliated Sixth People’s Hospital, Shanghai, China
Schizophrenia (SCZ) is a complex neuropsychiatric disorder, which is characterized by diverse symptoms, such as delusions, hallucinations, impaired motivation, social withdrawal, and cognitive impairment (Bowie et al. 2006; Joyce and Roiser 2007). It has a lifetime risk
Data Loading...
