Identification of rare genetic mutations in families with distinctive phenotypes

Abstract

Many psychiatric disorders are considered highly heritable, based on family or twin studies. Since their clinical diagnosis relies on interviews, each psychiatric disorder consists of a genetically and symptomatically heterogeneous population. To homogenize the disorder, we genetically analyzed patients with distinctive phenotypes encountered at the bedside. In this report, I present genetic analyses that were performed on a family with bipolar disorder that responded well to lithium carbonate and a family with schizophrenia and minor malformations and intellectual disability. Although each group consisted of only one family, we were able to successfully identify candidate disease mutations using the positional cloning method. The mutations were very rare and were predicted to strongly influence the onset of bipolar disorder and schizophrenia, respectively, from the onset. However, further functional analysis is required to confirm the implication of these gene products in the molecular pathology of these diseases.