Genome and Exome Analysis of Autistic Probands with Familial Aggregation of Psychiatric Disorders.

摘要

Autism is a pervasive developmental disorder typically characterized by repetitive behaviors, and deficits in social interaction and communication skills. Recent studies have linked autism with other psychiatric disorders, such as bipolar disorder, schizophrenia, major depression, and ADHD. Many of these disorders have been linked to alterations in similar genomic loci, and have demonstrated high heritability within families, especially among monozygotic (MZ) twins. The purpose of the current study was to first analyze the degree of psychiatric loading in families of individuals with autism; then, perform SNP genotyping on each autistic proband at two genes involved in the regulation of synaptic ion channels: CACNA1C and ANK3. Subsequently, one family was chosen for further analysis by whole exome sequencing to identify potentially causative mutations in genes that are suspected to be involved in neurodevelopmental processes. Potentially damaging variants in the following genes were identified in the autistic MZ twin probands and their parents: DISC1, AHI1, MAP7, SHANK2, and CNTNAP2. The results of this study support the premise that multiple inherited genetic factors may contribute to an autism phenotype in one individual, and that these factors may also contribute to psychiatric manifestations in other family members. As biotechnology advances, more holistic approaches to studying the genome, such as whole genome and exome sequencing, are being used in a clinical setting to aid in the diagnosis of many psychiatric disorders. With this in mind, it may be appropriate to examine each neuropsychiatric disorder more holistically, under the context of one cohesive neuronal mechanism.