Friday, May 8, 2009
Northwest Hall (Chicago Hilton)
10:00 AM
A. Crepel
,
Human Genetics, Center for Human Genetics, University of Leuven, Leuven, Belgium
J. Breckpot
,
Human Genetics, Center for Human Genetics, University of Leuven, Leuven, Belgium
J. P. Fryns
,
Human Genetics, Center for Human Genetics, University of Leuven, Leuven, Belgium
J. Steyaert
,
Department of Child Psychiatry, UPC-K.U.Leuven, 3000 Leuven, Belgium
K. Devriendt
,
Human Genetics, Center for Human Genetics, University of Leuven, Leuven, Belgium
H. Peeters
,
Human Genetics, Center for Human Genetics, University of Leuven, Leuven, Belgium
Background: A growing number of copy number variations (CNV) are detected in individuals with neurodevelopmental disorders. However, the interpretation is not always straightforward. Traditionally, causality is assumed when the CNV is not observed in the normal population and/or when it occurs
de novo or segregates with the disorder in the family. In addition, the presence of one or more genes in the CNV that can be linked to the pathogenesis of the phenotype may lend further support for causality.
Objectives: We describe the identification and delineation of a 2.2Mb microduplication in 1q42.2 in 2 brothers with autism and mild mental retardation and discuss the possible causal relation of this duplication to the autism phenotype.
Methods: The duplication was detected by Array-CGH with clones from the 1 Mb BAC/PAC clone set (Sanger Institute Hinxton, UK). The aberration was further delineated to 2.2Mb with a full-tiling BAC array containing the chromosome 1 clones. By means of quantitative real-time PCR (qPCR) the breakpoints of the duplication were mapped and segregation in the family was investigated. qPCR was used to screen 260 patients with autism for DISC1 duplications.
Results: The 2.2Mb duplication was present in the proband, his affected brother and the apparently unaffected father and paternal grandmother. Since this duplication was not present in 1577 Belgian persons, it was considered as a rare variant. Within this region the most interesting gene with respect to autism is DISC1 (disrupted-in-schizophrenia 1) since it is known to be involved in schizophrenia and has recently been associated to autism and bipolar disorder. A group of 260 patients with autism was studied for the occurrence of DISC1 duplications. In this screen no additional duplications were found.
Conclusions: This study is a typical illustration of the difficult interpretation of causality of a rare variant in neuropsychiatric disease. We conclude that the DISC1 duplication is a rare variant that probably confers susceptibility for autism in the current family.
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