Structural Genomic Variation in Intellectual Disability

The genetic causes of mental retardation are highly heterogeneous and for a large proportion unknown. Mutations as well as large chromosomal abnormalities are known to contribute to mental retardation, and recently more subtle structural genomic variations have been shown to contribute significantly to this common and complex disorder. Genomic microarrays with increasing resolution levels have revealed the presence of rare de novo CNVs in approximately 15% of all mentally retarded patients. Microarray-based CNV screening is rapidly replacing conventional karyotyping in the diagnostic workflow, resulting in an increased diagnostic yield as well as biological insight into this disorder. In this chapter, an overview is given of the detection and interpretation of copy number variations in mental retardation, with a focus on diagnostic applications. In addition, a detailed protocol is provided for the diagnostic interpretation of copy-number variations in mental retardation.