Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations in ion channels have been found to cause a variety of mendelian genetic diseases, and polyglutamine repeat expansion is a newly recognized pathogenic mechanism that causes several rare, genetic, late-onset neurological syndromes. Polymorphic polyglutamine tracts are present in a recently described human, calcium-activated potassium channel, KCNN3 (also known as hKCa3), and alleles of this gene that contain longer repeats have been associated with schizophrenia. The physiological function of the channel is consistent with an etiological role in this disease; drugs designed to target this channel might therefore provide novel psychotherapeutics.
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PMID:A piece in the puzzle: an ion channel candidate gene for schizophrenia. 986 21

Genetic anticipation, a phenomenon characterized by increased severity of symptoms and earlier age at onset of a disease in successive generations, is believed to be present in schizophrenia. In several neurodegenerative diseases showing anticipation, the mutation causing the disease is an expanded trinucleotide repeat. Therefore, genes containing trinucleotide repeats prone to expansion have become a suitable family of candidate genes in schizophrenia. A human calcium-activated potassium channel gene (hSKCa3), possibly mapping to chromosome 22q11-13, a region previously linked to schizophrenia, was recently described. This gene contains two contiguous expressed CAG repeat stretches. Recently, long allelic variants of one of these CAG repeats were found to be overrepresented in schizophrenic patients compared to normal controls. In this study we attempted to replicate this result and to study the relationship between the length of this CAG repeat on the one hand and the severity and age at onset of the disease on the other hand. No association with the disease or correlation with the severity of schizophrenia was identified. In addition, hSKCa3 was mapped to chromosome 1. Our results do not support the involvement of this particular CAG repeat-containing gene in schizophrenia.
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PMID:Lack of association between the hSKCa3 channel gene CAG polymorphism and schizophrenia. 1020 35

We demonstrate a significant association between longer CAG repeats in the hKCa3/KCNN3 calcium-activated potassium channel gene and schizophrenia in Israeli Ashkenazi Jews. We genotyped alleles from 84 Israeli Jewish patients with schizophrenia and from 102 matched controls. The overall allele frequency distribution is significantly different in patients vs controls (P = 0.00017, Wilcoxon Rank Sum test), with patients showing greater lengths of the CAG repeat. Northern blots reveal substantial levels of approximately 9 kb and approximately 13 kb hKCa3/KCNN3transcripts in brain, striated muscle, spleen and lymph nodes. Within the brain, hKCa3/KCNN3transcripts are most abundantly expressed in the substantia nigra, lesser amounts are detected in the basal ganglia, amygdala, hippocampus and subthalamic nuclei, while little is seen in the cerebral cortex, cerebellum and thalamus. In situ hybridization reveals abundant hKCa3/KCNN3 message localized within the substantia nigra and ventral tegmental area, and along the distributions of dopaminergic neurons from these regions into the nigrostriatal and mesolimbic pathways. FISH analysis shows that hKCa3/KCNN3 is located on chromosome 1q21.
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PMID:hKCa3/KCNN3 potassium channel gene: association of longer CAG repeats with schizophrenia in Israeli Ashkenazi Jews, expression in human tissues and localization to chromosome 1q21. 1039 15

Chandy et al suggested that a novel human neuronal small conductance, calcium-activated potassium channel gene, KCNN3, might be a candidate for schizophrenia. The KCNN3 cDNA sequences contain two stretches of CAG trinucleotide repeats encoding two separate polyglutamine segments near the N-terminus of this channel protein. The second CAG repeat was found to be highly polymorphic in the Caucasian population from both Europe and USA. Upon comparing the allelic frequency distribution between schizophrenic patients and ethnically matched controls, a significant excess of longer CAG repeats in schizophrenic patients was observed. A similar result was obtained in a recent replication study by Bowen et al, performed in Caucasians from UK or Eire. These results suggest an association between the longer CAG repeat allele of the KCNN3 gene and schizophrenia susceptibility. To verify if similar results can be observed in the Chinese population, we carried out a case-control study to compare the allelic frequency distribution of the CAG repeat of the KCNN3 gene between 92 Chinese schizophrenic patients and 100 normal controls from Taiwan. No significant difference of the allelic frequency distribution of the second CAG repeats was detected between the two groups (Wilcoxon Rank Sum test, P = 0.664). In addition, no over-representation of CAG repeats longer than the mode (19 repeats) was found in the patients' group (Fisher's exact test, P = 0.739). Thus, our data do not support that the second polymorphic CAG repeat of the KCNN3 gene may have an association with schizophrenia in our population.
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PMID:Genetic association study of a polymorphic CAG repeats array of calcium-activated potassium channel (KCNN3) gene and schizophrenia among the Chinese population from Taiwan. 1039 18

The human calcium-activated potassium channel gene (hKCNN3, hSKCa3) contains two tandemly arranged, multiallelic CAG repeats located in exon 1 which result in short to moderate polyglutamine stretches of unknown functional significance. Case-control and family-based association studies suggested an association of hKCNN3 repeats with susceptibility for schizophrenia. Twelve multiplex pedigrees with periodic catatonia, a schizophrenia subtype with major gene effect and patterns of anticipation, were genotyped using the multiallelic hKCNN3 repeat polymorphism. Using a dominant model of inheritance with sex- and age-dependent penetrance classes, cumulative results showed exclusion of linkage of hKCNN3 to periodic catatonia under the assumption of genetic homogeneity with lod score of -48.01 at zero recombination fraction. Our results provide evidence that hKCNN3 is not the causative gene in the familial schizophrenia subtype of periodic catatonia. By fluorescent in situ hybridization we confirmed the assignment of hKCNN3 to chromosome 1q21 near the heterochromatin region. Linkage mapping showed segregation with marker D1S498 (theta = 0.05) and placed hKCNN3 in the genetic linkage map in a cluster of genes near the centromeric region of chromosome 1.
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PMID:hKCNN3 which maps to chromosome 1q21 is not the causative gene in periodic catatonia, a familial subtype of schizophrenia. 1100 68

1. Recent developments in technologies permit systematic screening of the entire human genome as a strategy for identification of susceptibility genes of small effect that influence risk to complex traits, like schizophrenia (Schz), inflammatory bowel disease, bipolar affective disorder (BPAD) etc. 2. Schizophrenia is known to have a high heritability and a complex inheritance pattern. Several studies provide evidence that both genes and environment play a role in the etiology of schizophrenia. Linkage studies have observed racial and sex bias in the genetic constitution of schizophrenia. Schizophrenia also manifests clinical anticipation and genomic imprinting. 3. "Dynamic mutations" or "tandem repeat expansions" in DNA, explain a number of observations associated with clinical anticipation and genomic imprinting. In patient populations, the repeat expands well beyond the normal range, altering the biological function of the gene. These sequence are unstable and increase in size between family members in successive generations, giving rise to greater severity of disease. 4. Several workers have reported an association of trinucleotide repeat length with adult- and child-onset schizophrenia. One such expanded allele has been found at the CTG18.1 locus on the 18th chromosome. Other genes known to have similar mutation are SEF2-1, which codes for a helix-loop-helix protein, hSKCa3 gene, which codes for a calcium-activated potassium channel and the transthyretin gene. In schizophrenic patients, significant difference in allele frequency distribution of these genes has been reported. 5. Population based genetic research would not only help identify different subgroups of this of schizophrenia.
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PMID:Genetic basis of schizophrenia: trinucleotide repeats. An update. 1147 40

Schizophrenia is a chronic, debilitating psychotic illness of unknown etiology that has been the subject of many genetic studies. We studied the neonatal ventral-hippocampal lesioned rat as an animal model of schizophrenia in order to identify novel candidate genes for schizophrenia. Temporal and frontal cortices were assessed using cDNA microarrays for differences in mRNA expression associated with the lesion, haloperidol treatment and in two rat strains with differential sensitivity to the behavioural effects of the lesion. Genes that had altered expression levels as a result of the lesion, that were normalized by haloperidol treatment, and that differed between rat strains were selected. The pattern of differential transcription was confirmed with quantitative PCR for all six candidate genes: large conductance calcium-activated potassium channel, subfamily M, beta member 1 (Kcnmb1); doublecortex (dcx); adenylyl cyclase-associated protein 1 (CAP1); adenosine monophosphate deaminase 2-isoform L (AMPD2); malic enzyme 3, NADP(+)-dependent, mitochondrial (Me3); and aspartylglucosaminidase (AGA). None of these genes has been extensively studied in schizophrenia, and further work with post-mortem tissue and genetic studies are ongoing.
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PMID:Cortical gene expression in the neonatal ventral-hippocampal lesion rat model. 1589 Apr 97