DISC1 duplication in two brothers with autism and mild mental retardation

• Published in: Clinical genetics 2010-04, Vol.77 (4), p.389-394
• Main Authors: Crepel, A, Breckpot, J, Fryns, J-P, De la Marche, W, Steyaert, J, Devriendt, K, Peeters, H
• Format: Article
• Language: English
• Subjects: 1q42.2; Autism; Autistic Disorder - complications; Autistic Disorder - genetics; Biological and medical sciences; Child; Child clinical studies; Child, Preschool; Chromosome Aberrations; Chromosomes, Human, Pair 1 - genetics; Developmental disorders; DISC1; duplication; Family; Female; Fundamental and applied biological sciences. Psychology; Gene Duplication; General aspects. Genetic counseling; Genetic counseling; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genotype & phenotype; Humans; Infant, Newborn; Infantile autism; Intellectual Disability - complications; Intellectual Disability - genetics; Male; Medical genetics; Medical sciences; Mental retardation; Molecular and cellular biology; Nerve Tissue Proteins - genetics; Pedigree; Pregnancy; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Siblings
• ISSN: 0009-9163; 1399-0004
• DOI: 10.1111/j.1399-0004.2009.01318.x

Crepel A, Breckpot J, Fryns J‐P, De la Marche W, Steyaert J, Devriendt K, Peeters H. DISC1 duplication in two brothers with autism and mild mental retardation. We describe the identification and delineation of an inherited 2.07 Mb microduplication in 1q42.2 in two brothers with autism and mild mental retardation. Since this duplication was not present in 1577 Belgian persons, we consider this as an extremely rare variant which has the potential to provide further insight into the genetics of autism. The duplication contains seven genes including the DISC1 gene, an interesting candidate gene that has been associated to schizophrenia, bipolar disorder, autism and Asperger syndrome. In this report we describe additional analyses undertaken to investigate the causal relationship of the duplication to the autism phenotype. We conclude that the 1q42.2 microduplication probably confers susceptibility to autism in the current family. This study is a typical illustration of the difficult interpretation of causality of a very rare variant in neuropsychiatric disease and the challenge of genetic counselling in a particular family.