Mutations in human monoamine-related neurotransmitter pathway genes

被引:79
作者
Haavik, Jan [1 ]
Blau, Nenad [2 ]
Thoeny, Beat [2 ]
机构
[1] Univ Bergen, Dept Biomed, N-5020 Bergen, Norway
[2] Univ Childrens Hosp Zurich, Div Clin Chem & Biochem, Zurich, Switzerland
关键词
monoamine neurotransmitter; serotonin; catecholamine; dopamine; epinephrine; norepinephrine; psychiatric and neurological disorders; SNPs; haplotypes;
D O I
10.1002/humu.20700
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Biosynthesis and metabolism of serotonin and catecholamines involve at least eight individual enzymes that are mainly expressed in tissues derived from the neuroectoderm, e.g., the central nervous system (CNS), pineal gland, adrenal medulla, enterochromaffin tissue, sympathetic nerves, and ganglia. Some of the enzymes appear to have additional biological functions and are also expressed in the heart and various other internal organs. The biosynthetic enzymes are tyrosine hydroxylase (TH), tryptophan hydroxylases type 1 and 2 (TPH1, TPH2), aromatic amino acid decarboxylase (AADC), dopamine beta-hydroxylase (D beta H), and phenylethanolamine N-methyltransferase (PNMT), and the specific catabolic enzymes are monoamine oxidase A (MAO-A) and catechol O-methyltransferase (COMT). For the TH, DDC, DBH, and MAOA genes, many single nucleotide polymorphisms (SNPs) with unknown function, and small but increasing numbers of cases with autosomal recessive mutations have been recognized. For the remaining genes (TPH1, TPH2, PNMT, and COMT) several different genetic markers have been suggested to be associated with regulation of mood, pain perception, and aggression, as well as psychiatric disturbances such as schizophrenia, depression, suicidality, and attention deficit/hyperactivity disorder. The genetic markers may either have a functional role of their own, or be closely linked to other unknown functional variants. In the future, molecular testing may become important for the diagnosis of such conditions. Here we present an overview on mutations and polymorphisms in the group of genes encoding monoamine neurotransmitter metabolizing enzymes. At the same time we propose a unified nomenclature for the nucleic acid aberrations in these genes. New variations or details on mutations will be updated in the Pediatric Neurotransmitter Disorder Data Base (PNDDB) database (www.bioPKU.org).
引用
收藏
页码:891 / 902
页数:12
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