Schizophrenia and affective disorders - Cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: Clinical and P300 findings in a family
Schizophrenia and affective disorders - Cosegregation with a translocation at chromosome 1q42 that directly disrupts brain-expressed genes: Clinical and P300 findings in a family
复制标题
DOI：
10.1086/321969
复制
发表时间：
2001-08-01
影响因子：
9.8
通讯作者：
Muir, WJ
中科院分区：
文献类型：
--
作者：
Blackwood, DHR;Fordyce, A;Muir, WJ
一个家庭有一个（1; 11）（q42; q14.3）易位与包括精神分裂症和情感障碍的临床表型显著相关。当疾病表型仅限于精神分裂症时，这种易位产生的LOD评分为3.6，当疾病表型仅限于情感障碍时，LOD评分为4.5，当患有复发性重度抑郁症、双相情感障碍或精神分裂症的亲属都被归类为受影响时，LOD评分为7.1。这种联系的证据是精神疾病报道中最有力的证据之一。家庭成员没有表现出明显的特征，精神病表型可以区分无关的情况下，无论是精神分裂症或情感障碍，没有身体，神经，或畸形的条件共同发生的精神症状。易位携带者和非携带者的平均智商相同。易位携带者与精神分裂症受试者相似，与非携带者和对照组不同，表现为P300事件相关电位（ERP）振幅显著降低。此外，P300的振幅减少和潜伏期延长，测量在一些携带者的易位谁没有精神病性精神分裂症的其他家庭中发现的模式与多个成员的精神分裂症，其中P300的振幅和潜伏期似乎是特质标记的风险。这个家庭的核型，临床和ERP调查的结果表明，最近描述的基因DISC 1和DISC 2，这是直接破坏染色体1上的断点，可能有一个疾病表型的发展，包括精神分裂症以及单极和双相情感障碍的作用。
A family with a (1;11)(q42;q14.3) translocation significantly linked to a clinical phenotype that includes schizophrenia and affective disorders is described. This translocation generates a LOD score of 3.6 when the disease phenotype is restricted to schizophrenia, of 4.5 when the disease phenotype is restricted to affective disorders, of 7.1 when relatives with recurrent major depression, with bipolar disorder, or with schizophrenia are all classed as affected. This evidence for linkage is among the strongest reported for a psychiatric disorder. Family members showed no distinctive features by which the psychiatric phenotype could be distinguished from unrelated cases of either schizophrenia or affective disorders, and no physical, neurological, or dysmorphic conditions co-occurred with psychiatric symptoms. Translocation carriers and noncarriers had the same mean intelligence quotient. Translocation carriers were similar to subjects with schizophrenia and different from noncarriers and controls, in showing a significant reduction in the amplitude of the P300 event-related potential (ERP). Furthermore, P300 amplitude reduction and latency prolongation were measured in some carriers of the translocation who had no psychiatric symptoms-a pattern found in other families with multiple members with schizophrenia, in which amplitude of and latency of P300 appear to be trait markers of risk. The results of karyotypic, clinical, and ERP investigations of this family suggest that the recently described genes DISC1 and DISC2, which are directly disrupted by the breakpoint on chromosome 1, may have a role in the development of a disease phenotype that includes schizophrenia as well as unipolar and bipolar affective disorders.