Anticipation, imprinting, trinucleotide repeat expansions and psychoses.
1. Since 1991, approximately 20 trinucleotide repeat expansion type neurodegenerative disorders have been reported. They are clinically characterized by anticipation, i.e., worsening severity or earlier age at onset with each succeeding generation for an inherited disease, and imprinting, i.e., a process whereby specific genes are differentially marked during parental gametogenesis, resulting in the differential expression of these genes in the embryo and adult. 2. The phenomenon of anticipation in psychoses has been pointed out since the 19th century; however, it was ignored because no one knew the genetic mechanism underlying this type of inheritance pattern at the time, and because of several possible biases. 3. The discovery of trinucleotide repeat expansion diseases has reawakened interest in the phenomenon of anticipation in psychiatric diseases. Anticipation has been confirmed in schizophrenia, mood disorders, and anxiety disorders in much more sophisticated manners, although still not perfectly. 4. Molecular approaches as well as clinical ones have been taken to reveal the involvement of trinucleotide repeat expansion mechanism in psychoses by means of direct analyses of candidate genes, RED and DIRECT. Most efforts have been made for CAG type trinucleotide repeats. So far, direct analyses have failed to reveal pathogenic gene(s). There were several positive RED data at first, however, nowadays there seems to be a tendency of much more negative results. The DIRECT results did not support trinucleotide repeat expansions mechanism in psychoses either. One plausable explanation for the 'false positive' result is the presence of CAG trinucleotide repeats which are highly polymorphic but not associated with an obvious abnormal phenotype. Screening for trinucleotide repeats other than ones of the CAG type remained to be performed.
Clinical Research Institute, National Minami Hanamaki Hospital, Iwate, Japan.
K
K
Ohara
D020132:Anticipation, Genetic; D001008:Anxiety Disorders / Q000235:genetics; D005820:Genetic Testing; D018392:Genomic Imprinting; D006801:Humans; D019964:Mood Disorders / Q000235:genetics; D019636:Neurodegenerative Diseases / Q000235:genetics; D011618:Psychotic Disorders / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics; D019680:Trinucleotide Repeat Expansion