DISC1 duplication in two brothers with autism and mild mental retardation

Abstract

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.

Familial Duplication/Deletion of 1q42.13q43 as Meiotic Consequence of an Intrachromosomal Insertion in Chromosome 1

“…They found 477 insertional translocations with an incidence of approximately 2.1%, demonstrating that the frequency detected with array-CGH seems to be higher . This result is confirmed by some other recent studies which estimated the frequency of these rearrangements at the submicroscopic level by array-CGH [Bartsch et al, 2001;Williams et al, 2009;Crepel et al, 2010;Rigola et al, 2015;Morris et al, 2016;Wang et al, 2016].…”

“…Rearrangements of the region 1q42.13q43 are rare, with only 7 cases reported to date [Beemer et al, 1985;Bortotto et al, 1990;Kato et al, 2007;Williams et al, 2009;Crepel et al, 2010;Rigola et al, 2015;Wang et al, 2016]. The imbalances described are usually the result of inherited translocations involving other chromosomes, making difficult to establish a specific karyotype/phenotype correlation.…”

Evidence for association between Disrupted-in-schizophrenia 1 (DISC1) gene polymorphisms and autism in Chinese Han population: a family-based association study

“…Therefore, DISC1 was selected as a candidate gene for autism. Two reports have revealed some abnormalities of DISC1 in three individuals with autism spectrum disorders (ASD) [49,50]. Moreover, a Finnish group has represented a significant association of DISC1 with ASD.…”

The 1000 Genomes Project: deep genomic sequencing waiting for deep psychiatric phenotyping

“…For example, 22q11 deletion was initially found to be overrepresented in patients with schizophrenia, 4 mood disorders, 5 anxiety disorders and attention-deficit/ hyperactivity disorder, 6 pervasive developmental disorders and various levels of intellectual deficit. 5,8,9 The same pattern of indiscriminate association of many psychiatric phenotypes (e.g., mental retardation, schizophrenia, autism) and neurologic disorders (e.g., epilepsy) with chromosomal variants (e.g., translocation disrupting DISC1 [10][11][12][13] ) and copy number variations (CNVs) [14][15][16][17] is increasingly reported as investigators search for these rare variants in patients with various disorders or in carriers of a specific rare variant. Also, rare single point mutations that potentially disturb gene functions have been reported in several psychiatric phenotypes.…”