New genetic hypothesis of schizophrenia

Lack of complete concordance for schizophrenia in monozygotic twins has bee n interpreted as indicative of non-genetic cofactors in transmission of the illness. We present an alternative hypothesis that can parsimoniously expl ain, using known genetic mechanisms, the heredity pattern, the phenotypic s pectrum and the biological abnormalities found in schizophrenia. The inheri tance of a single recessive mutated allele of a gene crucial in brain devel opment if followed by a somatic mutation in the normal allele during critic al periods of brain development could result in developmental abnormalities that are expressed behaviorally as schizophrenic illness. Acquisition of t his somatic mutation is likely enhanced during periods of intense cell divi sion; therefore, the window of opportunity would be restricted to key perio ds in neurodevelopment. The somatic mutation may not always occur, thus exp laining the variability of expression seen in the clinical population. Beca use the single allele mutation is still transmissible, the equal incidence of schizophrenia in the offspring of monozygotic twins discordant for the d isease could also be explained. This possibility has implications for the d evelopment of genetic models and the source of genetic material for studies isolating the gene(s) of schizophrenia.