Identification of somatic mutations in monozygotic twins discordant for psychiatric disorders

• Published in: NPJ schizophrenia Vol. 4; no. 1; p. 7
• Main Authors: Nishioka, Masaki, Bundo, Miki, Ueda, Junko, Yoshikawa, Akane, Nishimura, Fumichika, Sasaki, Tsukasa, Kakiuchi, Chihiro, Kasai, Kiyoto, Kato, Tadafumi, Iwamoto, Kazuya
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.04.2018; Nature Publishing Group
• Subjects: 631/136; 692/699/476/1761; 692/699/476/1799; Behavior disorders; Cognitive Psychology; Medicine; Medicine & Public Health; Mental disorders; Mutation; Neurology; Neurosciences; Psychiatry; Twins
• ISSN: 2334-265X; 2334-265X
• DOI: 10.1038/s41537-018-0049-5

Monozygotic twins are assumed to have identical genomes. Based on this assumption, phenotypic discordance in monozygotic twins has been previously attributed to environmental factors. However, recent genomic studies have identified characteristic somatic mutations in monozygotic twins discordant for Darier disease, Van der Woude syndrome, and Dravet syndrome. Here, we explored somatic mutations in four pairs of monozygotic twins discordant for schizophrenia or delusional disorder. We analyzed whole exome sequence data obtained from blood samples and identified seven somatic mutations in one twin pair discordant for delusional disorder. All seven of these mutations were validated by independent amplicon sequencing, and five of them were further validated by pyrosequencing. One somatic mutation in the patient with delusional disorder showed a missense variant in ABCC9 with an allele fraction of 7.32%. Although an association between the somatic mutations and phenotypic discordance could not be established conclusively in this study, our results suggest that somatic mutations in monozygotic twins may contribute to the development of psychiatric disorders, and can serve as high-priority candidates for genetic studies. Genetics: Identical twins can still differ genetically, with impacts on psychosis Identical twins are not always identical when it comes to psychiatric disorders—and DNA mutations that arise after birth could explain why. Researchers in Japan led by Tadafumi Kato from the RIKEN Brain Science Institute and 
Kazuya Iwamoto from Kumamoto University searched for DNA differences between four pairs of identical twins discordant for schizophrenia or delusional disorder by sequencing the entire protein-coding portion of the genome from the study subjects’ blood. In one sibling pair, they found seven genetic differences, including one in the sister with the delusional disorder that altered the sequence of a protein implicated in sleep and other brain functions. The findings suggest that, alongside epigenetic and environmental differences, acquired mutations can account for discordances in psychiatric illnesses among otherwise genetically identical twins.