Candidate gene study on schizophrenia

筛选位于22q11上的PNUTL、GP1Bβ、WDR14和TBX1基因进行多态性检测。PNUTL、GP1Bβ、WDR14、TBX1分别有1个、3个、4个多态性。这些变异的病例对照研究使用了200名精神分裂症患者和199名对照者。-85C b> G和928G>A的等位基因频率在病例与对照组之间差异显著（-85C>G的等位基因频率P=0.0074,OR = 1.57,95%CI=1.08-2.32; 928G>A的等位基因频率P=0.019，OR=0.36,95%CI=0.04-0.77）。-85G/G组患者的平均发病年龄明显低于-85C/ G组（P=0.05）。这些数据表明-85C >g可能与精神分裂症的易感性有关。我们对携带-85C/C和-85G/G的精神分裂症患者进行威斯康星卡片分类测试（WCST）。-85G/G组患者的错误评分明显高于-85C/C组。提示TBX1基因可能是精神分裂症易感性的遗传危险因素，与大脑额叶皮质功能有关。发现有1例精神分裂症患者携带t(4p,13q)(16.1; 21.31)，兄弟姐妹携带inv(9)(p11,q13) （Itokawa等）。心理临床神经科学2004)。易位父母的细胞遗传学分析显示无易位，患者为新生易位。4p16.1是Wolfram综合征的WFS1基因位点，60%的病例表现为精神病症状。13q21.31位点也被报道为精神分裂症易感区位点。我们现在正在进行FISH分析，以检测在4p16.1或13q21.31的断点上的基因。携带inv(9)（p11,q13）的兄弟姐妹都患有精神分裂症，而且他们都是患有精神分裂症的儿童。他们的母亲也患有精神分裂症，10年前因肾衰竭去世。我们现在正在调查第三个孩子，以检查核型。如果三个孩子都有倒置9，我们会跟进母亲的家庭。

The PNUTL, GP1Bβ, WDR14 and TBX1,which are located on 22q11,were screened for detection of polymorphisms. A polimorphism in PNUTL,3 in GP1Bβ, 4 in WDR14,and 16 in TBX1 were detected. Case control studies of those variations were performed using 200 schizophrenia and 199 controls. Allelic frequencies of the -85C>G and 928G>A were significantly different between case and controls (P=0.0074,OR1.57,95%CI=1.08-2.32 for the -85C>G and P=0.019,OR=0.36,95%CI=0.04-0.77 for the 928G>A). Average of age of onset was significantly low in patients with -85G/G compared with that with -85C/C (P=0.05). Those data suggested that -85C>G may be involved in susceptibility for schizophrenia. We performed Wisconcin Card Sorting Test (WCST) with schisophrenics carrying -85C/C and -85G/G. Patients with -85G/G showed significantly high error score as compared with that with -85C/C. It was suggested that TBX1 gene may be genetic risk factor for predisposing to schizophrenia and involved in brain function of frontal cortex.A schizophrenia having t(4p,13q)(16.1; 21.31) and sib pair with schizophrenia carrying inv(9)(p11,q13) were detected (Itokawa et al. Pshciatry Clin neurosci 2004). Cytogenetic analyses of parents of translocation showed no translocation and the patients is de novo translocation. The 4p16.1 is the locus of WFS1 gene for Wolfram syndrome, which shows psychotic symptoms in 60% of the cases. The 13q21.31 is also reported as the locus of susceptible reagion for schizophrenia. We are now performing FISH analysis for detection a gene in the break point on 4p16.1 or 13q21.31. The sib pair carrying inv(9)(p11,q13) are both schizophrenia and moreover are children who all suffer from schizophrenia. Their mother is also schizophrenia who died by renal failure 10 years ago. We are now investigating third child in order to check karyotype. If three children share inversion 9,we will follow up mother's family.