Psychiatric aspects of chromosomal microdeletions and trinucleotide repeats

Current Opinion in Psychiatry

Volumn 11, Issue 4, 1998, Pages 373-378

  Skuse, David H ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

BRAIN DEVELOPMENT; BRAIN FUNCTION; CHROMOSOME DELETION; GENE ISOLATION; GENE LOCUS; GENOME; HUMAN; MENTAL DISEASE; MENTAL RETARDATION MALFORMATION SYNDROME; PSYCHIATRY; REVIEW; TRINUCLEOTIDE REPEAT;

EID: 0031826437     PISSN: 09517367     EISSN: None     Source Type: Journal    
DOI: 10.1097/00001504-199807000-00002     Document Type: Review

References (66)

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50. •] cosegregated with poor visuospatial skills in two families. They hypothesized that Williams syndrome was a contiguous gene deletion syndrome in which a typical cognitive profile includes a weakness in pattern construction and a strength in digit recall relative to performance on other nonverbal subtests. They tested the specific hypothesis that hemizygosity of a gene encoding a protein kinase which lay immediately 3 of the elastin gene ELN could be responsible for the cognitive profile, because mouse models with protein kinase gene disruption had already been shown to have impaired visuospatial skills. LIMK1 (which is expressed widely in the cerebral cortex) mapped close to ELN locus, and in individuals with the partial syndrome the deletion extended to inlude that locus as well. Individuals with autosomal dominant supravalvular aortic stenosis only, in whom only the ELN gene was deleted (this gene is not expressed in the brain).
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64. Chandy KG, Fantino E, Wittekindt O, Kalman K, Tong L-L, Ho T-H, et al. Isolation of a novel potassium channel gene hKCa3 containing a polymorphic CAG repeat: a candidate for schizophrenia or bipolar disorder? Mol Psychiatry 1998; 3:32-37. The human gene for the neuronal small conductance calcium-activated potassium channel (hSKCa3) has two in-frame CAG repeats, the second of which is highly polymorphic with allele sizes ranging in size from 12 to 28 repeats. hSKCaS maps to 22q11.2-q13.1, one of the putative susceptibility regions for schizophrenia and bipolar disease. The results presented here provide evidence of a possible association between longer alleles in the hSKCa3 gene and both disorders. Small conductance calcium-activated potassium channels play a critical role in determining the firing patterns of neurones.
65. Coming DE. Polygenic inheritance and micro/minisatellites. Mol Psychiatry 1998; 3:21-31. The author proposes that micro-and minisatellite polymorphisms play a role in the expression of many genes, and consequently those genes could exist in the population with many functional alleleomorphic variants. Any one individual may inherit a threshold number of functional variants beyond which there are appreciable effects on the phenotype. Varying length of trinucleotide repeat sequences may, it is proposed, affect gene function through a wide variety of mechanisms even when the number of repeats is apparently within the 'normal' range.
66. Andrew SE, Goldberg YP, Hayden MR. Rethinking genotype and phenotype correlations in polyglutamine expansion disorders. Hum Mol Genet 1997; 6:2005-2010. The possibility is discussed that diseases associated with triplet repeats (which have usually been regarded as influenced simply by mutation in the predisposing genetic locus) may show reduced penetrance in certain individuals, in some circumstances. What factors, other than the CAG size, contribute to the age of onset and influence penetrance rates? Could they be environmental? Could they be related to other genetic influences?