American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
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Am. J. Med. Genet. B Neuropsychiatr. Genet. · Sep 2007
Expression of multiple catechol-o-methyltransferase (COMT) mRNA variants in human brain.
Catechol-o-methyltransferase (COMT) is important for modulating dopamine levels, prefrontal cortex (PFC) function, and several psychiatric phenotypes. A single COMT mRNA has been described in human brain, which gives rise to membrane-bound (MB)- and soluble (S)-COMT proteins. In addition, we have recently described a novel COMT protein isoform in the human PFC, suggesting that there are more COMT gene products expressed than are currently appreciated. ⋯ The regional distributions of these transcripts are described. The results demonstrate multiple COMT mRNAs in human brain, revealing an additional complexity to the biology of COMT. The alternate gene products may be of significant functional importance, and differentially impacted by polymorphisms within the COMT gene.
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Am. J. Med. Genet. B Neuropsychiatr. Genet. · Jun 2007
Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly.
Mutations in the PTEN gene are associated with a broad spectrum of disorders, including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Lhermitte-Duclos disease. In addition, PTEN mutations have been described in a few patients with autism spectrum disorders (ASDs) and macrocephaly. In this study, we screened the PTEN gene for mutations and deletions in 88 patients with ASDs and macrocephaly (defined as >or=2 SD above the mean). ⋯ Polydactyly has previously been described in two patients with Lhermitte-Duclos disease and CS and is thus likely to be a rare sign of PTEN mutations. Our findings suggest that PTEN mutations are a relatively infrequent cause of ASDs with macrocephaly. Screening of PTEN mutations is warranted in patients with autism and pronounced macrocephaly, even in the absence of other features of PTEN-related tumor syndromes.
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Am. J. Med. Genet. B Neuropsychiatr. Genet. · Jul 2006
Three major haplotypes of the beta2 adrenergic receptor define psychological profile, blood pressure, and the risk for development of a common musculoskeletal pain disorder.
Adrenergic receptor beta(2) (ADRB2) is a primary target for epinephrine. It plays a critical role in mediating physiological and psychological responses to environmental stressors. Thus, functional genetic variants of ADRB2 will be associated with a complex array of psychological and physiological phenotypes. ⋯ We propose that the first haplotype codes for lower levels of ADRB2 expression, the second haplotype codes for higher ADRB2 expression, and the third haplotype codes for higher receptor expression and rapid agonist-induced internalization. Individuals who carried one haplotype coding for high and one coding for low ADRB2 expression displayed the highest positive psychological traits, had higher levels of resting arterial pressure, and were about 10 times less likely to develop TMD. Thus, our data suggest that either positive or negative imbalances in ADRB2 function increase the vulnerability to chronic pain conditions such as TMD through different etiological pathways that imply the need for tailored treatment options.
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Am. J. Med. Genet. B Neuropsychiatr. Genet. · Apr 2006
The CACNA1A and ATP1A2 genes are not involved in dominantly inherited migraine with aura.
Epidemiological studies indicate that migraine with typical aura (MA) has a major genetic component but the genes for MA have not been identified. However, the autosomal dominantly inherited familial hemiplegic migraine (FHM) is often caused by mutations in the CACNA1A or ATP1A2 genes. The aim of the study was to investigate if the CACNA1A or ATP1A2 genes are involved in MA with an apparently autosomal dominant mode of inheritance. ⋯ No polymorphism was identified in the CACNA1A or ATP1A2 genes with a strong correlation to MA. Our study shows that the CACNA1A or ATP1A2 genes are probably not involved in MA. To identify the genes involved in the common forms of migraine, future genetic studies should focus on MA and migraine without aura (MO) and not FHM.
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Am. J. Med. Genet. B Neuropsychiatr. Genet. · Jul 2005
Biography Historical ArticleISPG Lifetime Achievement Award 2004.