• 作者：Thorsten M. Kranz^a ; ^{Thorsten.kranz@nyumc.org" class="auth_mail" title="E-mail the corresponding author} ; Adam Berns^b ; ^{Adam.berns@med.nyu.edu" class="auth_mail" title="E-mail the corresponding author} ; Jerry Shields^b ; ^{jeshields@chpnet.org" class="auth_mail" title="E-mail the corresponding author} ; Karen Rothman^b ; ^{Karen.rothman@nyumc.org" class="auth_mail" title="E-mail the corresponding author} ; Julie Walsh-Messinger^c ; ^{jmessinger1@udayton.edu" class="auth_mail" title="E-mail the corresponding author} ; Raymond R. Goetz^d ; ^{Goetzra@nyspi.columbia.edu" class="auth_mail" title="E-mail the corresponding author} ; Moses V. Chao^a ; ^{Moses.chao@med.nyu.edu" class="auth_mail" title="E-mail the corresponding author} ; Dolores Malaspina^b ; ^{Dolores.malaspina@nyumc.org" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Human genetics ; Schizophrenia ; Neurotrophins ; Psychosis ; Endophenotype ; Diagnosis ; ARMS/KIDINS220
• 刊名：EBioMedicine
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：6
• 期：Complete
• 页码：206-214
• 全文大小：830 K

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Rare gene variants and new mutations are important components of the genetic susceptibility to schizophrenia.

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Targeted exome capture of a gene panel revealed de novo mutations and rare missense coding polymorphisms in four genes among 48 new schizophrenia cases.

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These affected genes are: PTPRG (Protein Tyrosine Phosphatase, Receptor Type G), SLC39A13 (Solute Carrier Family 39 (Zinc Transporter) Member 13), TGM5 (Transglutaminase 5), ARMS/KIDINS220 (Ankyrin repeat-rich membrane spanning protein or Kinase D-Interacting Substrate of 220 kDa).

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One or more additional rare missense coding polymorphisms in any of these genes were identified in 31% of the sample (15 cases).

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Significant phenotypic differences existed among the subgroups of cases harboring genetic variants in these genes.

A challenge in schizophrenia is individual differences with respect to etiology and optimum treatments. Of note, rare gene variants are important components of schizophrenia susceptibility. These can arise as new mutations in the paternal germline and their number can increase with age and get transmitted to future generations. This study focused on four genes, which have previously shown to carry rare missense coding variants among two independent schizophrenia cohorts. Four or five missense coding polymorphisms or novel mutations across these genes occurred in 15/48 clinically intensively characterized cases, with some cases harboring two of these genes. Subgrouping cases by which gene displayed rare missense coding polymorphisms or novel mutations revealed differences in cognition, symptoms and clinical features. These may be relevant to person specific treatments.