Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038379 (strabismus)
 9,317 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The increased incidence of minor physical anomalies (MPAs) in schizophrenia is the fundamental basis for the neurodevelopmental hypothesis of schizophrenia etiology. Ocular misalignment, or strabismus, falls into the category of MPAs, but this phenotype has not been assessed in schizophrenia. This study reveals that a subtype of strabismus, constant exotropia, displays marked association with schizophrenia (P=0.00000000906). To assess the genetic mechanisms, we examined the transcription factor genes ARIX (recently identified as a causative gene for syndromic strabismus) and its paralogue, PMX2B. We identified frequent deletion/insertion polymorphisms in the 20-alanine homopolymer stretch of PMX2B, with a modest association between these functional polymorphisms and constant exotropia in schizophrenia (P=0.029). The polymorphisms were also associated with overall schizophrenia (P=0.012) and more specifically with schizophrenia manifesting strabismus (P=0.004). These results suggest a possible interaction between PMX2B and other schizophrenia-precipitating factors, increasing the risk of the combined phenotypes. This study also highlights the unique nature of the polyalanine length variations found in PMX2B. In contrast with other transcription factor genes, the variations in PMX2B show a high prevalence, with deletions being more common than insertions. Additionally, the polymorphisms are of ancient origin and stably transmitted, with mild phenotypic effects. In summary, our study lends further support to the disruption of neurodevelopment in the etiology of schizophrenia, by demonstrating the association of a specific MPA, in this case, constant exotropia with schizophrenia, along with molecular variations in a possible causative gene.
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PMID:Association between schizophrenia with ocular misalignment and polyalanine length variation in PMX2B. 1470 96

The increased incidence of minor physical anomalies (MPAs) in schizophrenia is the fundamental basis for the neurodevelopmental hypothesis of schizophrenia etiology. Ocular misalignment falls into the category of MPAs, but this phenotype has not been assessed in schizophrenia. This study reveals that constant exotropia displays marked association with schizophrenia. To assess the genetic mechanisms, we examined the transcription factor genes ARIX and its paralogue, PMX2B. We identified frequent deletion/insertion polymorphisms in the 20-alanine homopolymer stretch of PMX2B, with a modest association between these functional polymorphisms and constant exotropia in schizophrenia. The polymorphisms were also associated with overall schizophrenia and more specifically with schizophrenia manifesting strabismus. These results suggest a possible interaction between PMX2B and other schizophrenia-precipitating factors, increasing the risk of the combined phenotypes. This study also highlights the unique nature of the polyalanine length variations found in PMX2B.
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PMID:[Schizophrenia and ocular misalignment: phenotypic and genetic association analysis]. 1577 Sep 61

The 22q11.2 deletion is the most prominent known genetic risk factor for schizophrenia, but its penetrance is at most approximately 50% suggesting that additional risk factors are required for disease progression. We examined a woman with schizophrenia with this deletion for such risk factors. She had high plasma pentosidine levels ('carbonyl stress') and a frameshift mutation in the responsible gene, GLO1. She also had a constant exotropia, so we examined the PHOX2B gene associated with both schizophrenia and strabismus, and detected a 5-alanine deletion. We propose that the combination of these genetic defects may have exceeded the threshold for the manifestation of schizophrenia.
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PMID:Schizophrenia with the 22q11.2 deletion and additional genetic defects: case history. 2188 Oct 99