Candidate genes and the behavioral phenotype in 22q11.2 deletion syndrome.
There is an overwhelming evidence that children and adults with 22q11.2 deletion syndrome (22q11.2DS) have a characteristic behavioral phenotype. In particular, there is a growing body of evidence that indicates an unequivocal association between 22q11.2DS and schizophrenia, especially in adulthood. Deletion of 22q11.2 is the third highest risk for the development of schizophrenia, with only a greater risk conferred by being the child of two parents with schizophrenia or the monozygotic co-twin of an affected individual. Both linkage and association studies of people with schizophrenia have implicated several susceptibility genes, of which three are in the 22q11.2 region; catechol-o-methyltransferase (COMT), proline dehydrogenase (PRODH), and Gnb1L. In addition, variation in Gnb1L is associated with the presence of psychosis in males with 22q11.2DS. In mouse models of 22q11.2DS, haploinsufficiency of Tbx1 and Gnb1L is associated with reduced prepulse inhibition, a schizophrenia endophenotype. The study of 22q11.2DS provides an attractive model to increase our understanding of the development and pathogenesis of schizophrenia and other psychiatric disorders in 22q11.2DS and in wider population.
Prasad
Sarah E
SE
Department of Psychiatry, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Republic of Ireland. sprasad@rcsi.ie
Howley
Sarah
S
Murphy
Kieran C
KC
D000328:Adult; D000818:Animals; D002394:Catechol O-Methyltransferase / Q000235:genetics; D002648:Child; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics*; D004062:DiGeorge Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D004200:Diseases in Twins / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D051379:Mice; D008957:Models, Genetic; D010641:Phenotype; D011394:Proline Oxidase / Q000235:genetics; D011618:Psychotic Disorders / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D020825:T-Box Domain Proteins / Q000235:genetics
C434113:GNB1L protein, human; D005819:Genetic Markers; D047908:Intracellular Signaling Peptides and Proteins; D020825:T-Box Domain Proteins; C108625:TBX1 protein, human; D011394:Proline Oxidase; D002394:Catechol O-Methyltransferase