| 1 | Neurosci. Res. 2001 Jun 40: 105-13 |
|---|---|
| PMID | 11377748 |
| Title | Molecular genetics of bipolar disorder. |
| Abstract | Alteration of monoaminergic neurotransmission is implicated in the pathophysiology of bipolar disorder (manic-depressive illness). Candidate genes participating in monoaminergic neurotransmission, especially serotonin transporter and monoamine oxidase A, may be associated with bipolar disorder. And the regulating regions of these genes and the molecules participating in intracellular signal transduction are now under investigation. To date, 13 whole genome positional cloning studies have been performed and many candidate loci identified. Using patients from a pedigree in which schizophrenia, depression or bipolar disorder have been linked with a balanced translocation at 1 and 11, candidate pathogenetic genes were cloned as DISC1 (disrupted in schizophrenia-1) and DISC2. Recently, pathogenetic mutations have been identified in two genetic diseases frequently co-morbid with mood disorder; WFS1 for Wolfram syndrome and ATP2A2 (SERCA2) for Darier's disease. Transmission of bipolar disorder may be characterized by anticipation and parent-of-origin effect, and extended CTG repeat at SEF2-1B gene was identified from a bipolar patient. However, its pathogenetic role was not supported by subsequent studies. Association of bipolar disorder with mitochondrial DNA has also been suggested. The role of genomic imprinting is also possible because linkage to 18p11 is limited to paternally transmitted pedigrees. These results warrant further study of molecular genetics of bipolar disorder. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | Psychiatr. Genet. 2003 Mar 13: 29-32 |
| PMID | 12605098 |
| Title | The WFS1 (Wolfram syndrome 1) is not a major susceptibility gene for the development of psychiatric disorders. |
| Abstract | Wolfram syndrome is a neurodegenerative disorder that is inherited in an autosomal recessive mode and characterized by the presence of diabetes mellitus and optic atrophy. Patients and heterozygote carriers are at an increased risk of suffering psychiatric disorders. Mutations in the Wolfram gene (WFS1 ) (4p16.1) are responsible for the development of the disease, and mRNA and protein expression of WFS1 have recently been found in areas of the rat brain that can be related to the psychiatric symptoms. To test the hypothesis that WFS1 mutations in heterozygote carriers or other variants of WFS1 can predispose to mental illness. Stage 1: Exons 2, 4 and 8 of that harbour mutations in Spanish Wolfram syndrome families were examined by Single Strand Conformation Polymorphism and sequencing analysis in 43 patients with affective disorder to identify variants and mutations. Stage 2: two variants identified in stage 1 were analysed in 152 psychiatric patients (118 schizophrenia and 34 affective disorder) and 177 control subjects. Six variants (I333V Ile-->Val, F341, N500, R708, K774, K811) and a WFS1 mutation (R818C, Arg-->Cys) were found in the 43 patients analysed in stage 1 of the study. In stage 2, the R818C mutation was not found in the group of psychiatric patients but it was present in one control subject. The association study conducted with the I333V variant did not find significant differences in allele or genotype frequencies between patients and control subjects. Our results suggest that WFS1 is not a major susceptibility gene for the development of psychiatric disorders in our population. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Neurosci. Lett. 2003 Feb 338: 21-4 |
| PMID | 12565131 |
| Title | No association of mutations and mRNA expression of WFS1/wolframin with bipolar disorder in humans. |
| Abstract | Association of WFS1 (wolframin) and bipolar disorder has been suggested by psychiatric manifestations in patients or non-symptomatic carriers of Wolfram disease and linkage of bipolar disorder with 4p16, the locus of WFS1. Five studies of WFS1 in bipolar disorder did not support this association, although possible association of several missense mutations has not been excluded yet. In this study, four such mutations were genotyped in 184 patients with bipolar disorder and 207 controls. None had the A559T and A602V mutations, and no association of G576S and H611R with bipolar disorder was found. We also quantified the expression levels of WFS1 mRNA in the postmortem brains of patients with bipolar disorder, depression, schizophrenia, and controls. There was no significant difference of the expression levels. These results did not support the pathophysiological significance of WFS1 in bipolar disorder. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Psychiatry Clin. Neurosci. 2004 Jun 58: 333-7 |
| PMID | 15149303 |
| Title | Identification of a male schizophrenic patient carrying a de novo balanced translocation, t(4; 13)(p16.1; q21.31). |
| Abstract | Herein is reported the case of a male patient with schizophrenia who displayed a de novo balanced translocation between the short arm of chromosome 4 and the long arm of chromosome 13, t(4; 13)(p16.1; q21.31). The 4p16.1 region is where the causative gene (WFS1) for Wolfram syndrome has been mapped. In Wolfram syndrome, approximately 60% of patients suffer from major mental illness. The other breakpoint, chromosome 13q21.31, is another region where previous linkage studies have repeatedly detected linkage to schizophrenia. The documentation of the present case could therefore provide a valuable resource for identifying disease susceptibility genes by localizing the breakpoints. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 5 | Psychiatry Clin. Neurosci. 2004 Jun 58: 333-7 |
| PMID | 15149303 |
| Title | Identification of a male schizophrenic patient carrying a de novo balanced translocation, t(4; 13)(p16.1; q21.31). |
| Abstract | Herein is reported the case of a male patient with schizophrenia who displayed a de novo balanced translocation between the short arm of chromosome 4 and the long arm of chromosome 13, t(4; 13)(p16.1; q21.31). The 4p16.1 region is where the causative gene (WFS1) for Wolfram syndrome has been mapped. In Wolfram syndrome, approximately 60% of patients suffer from major mental illness. The other breakpoint, chromosome 13q21.31, is another region where previous linkage studies have repeatedly detected linkage to schizophrenia. The documentation of the present case could therefore provide a valuable resource for identifying disease susceptibility genes by localizing the breakpoints. |
| SCZ Keywords | schizophrenia, schizophrenic |