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)

We investigated the involvement of rare (<1%) copy number variants (CNVs) in 471 cases of schizophrenia and 2792 controls that had been genotyped using the Affymetrix GeneChip 500K Mapping Array. Large CNVs >1 Mb were 2.26 times more common in cases (P = 0.00027), with the effect coming mostly from deletions (odds ratio, OR = 4.53, P = 0.00013) although duplications were also more common (OR = 1.71, P = 0.04). Two large deletions were found in two cases each, but in no controls: a deletion at 22q11.2 known to be a susceptibility factor for schizophrenia and a deletion on 17p12, at 14.0-15.4 Mb. The latter is known to cause hereditary neuropathy with liability to pressure palsies. The same deletion was found in 6 of 4618 (0.13%) cases and 6 of 36 092 (0.017%) controls in the re-analysed data of two recent large CNV studies of schizophrenia (OR = 7.82, P = 0.001), with the combined significance level for all three studies achieving P = 5 x 10(-5). One large duplication on 16p13.1, which has been previously implicated as a susceptibility factor for autism, was found in three cases and six controls (0.6% versus 0.2%, OR = 2.98, P = 0.13). We also provide the first support for a recently reported association between deletions at 15q11.2 and schizophrenia (P = 0.026). This study confirms the involvement of rare CNVs in the pathogenesis of schizophrenia and contributes to the growing list of specific CNVs that are implicated.
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PMID:Support for the involvement of large copy number variants in the pathogenesis of schizophrenia. 1918 81

Background: Schizophrenic disorders are common and debilitating due to their symptoms, which can include delusions, hallucinations, and other negative symptoms. Organic forms can result from various cerebral disorders. In this paper, we discuss a potential association between schizophrenia and hereditary polyneuropathies (PNPs). Case presentation: We present the case of a 55-year-old female patient with chronically paranoid-hallucinatory schizophrenia, severe cognitive deficits since the age of 30, and comorbid repeated focal pressure neuropathies beginning at age 20. At the age of 35, genetic testing revealed a deletion on chromosome 17p12 covering the peripheral myelin protein 22 gene (PMP22), which led to the diagnosis of hereditary neuropathy with liability to pressure palsy (HNPP). Cerebral magnetic resonance imaging showed internal atrophy, magnetic resonance spectroscopy found alteration of the glutamate and myo-inositol levels in the anterior cingulate cortex, neuropsychological testing showed deficits in working memory and psychomotor speed, and electrophysiological testing detected signs of sensorimotor demyelinating PNP (accentuated in the legs). Conclusion: There may be an association between schizophrenia and HNPP. In observational studies, the deletion of interest (chromosome 17p12) was nearly 10 times more common in schizophreniform patients than in controls. This potential association could be pathophysiologically explained by the role of PMP22, which is mainly expressed in the peripheral nervous system. However, PMP22 mRNA and protein can also be found in the brain. PMP22 seems to play an important role in regulating cell growth and myelination, functions that are disturbed in schizophrenia. Such a connection obviously cannot be clarified on the basis of one case. Future studies should analyze whether patients with HNPP exhibit increased rates of psychotic disorders, and patients with schizophrenia and repeated focal pressure neuropathies should be examined for the PMP22 mutation. Alternatively, the co-occurrence of schizophrenia and HNPP could be coincidental.
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PMID:Schizophrenia and Hereditary Polyneuropathy: PMP22 Deletion as a Common Pathophysiological Link? 3111 6