A 15q13.3 microdeletion segregating with autism

Abstract

Autism and mental retardation (MR) show high rates of comorbidity and potentially share genetic risk factors. In this study, a rare approximately 2 Mb microdeletion involving chromosome band 15q13.3 was detected in a multiplex autism family. This genomic loss lies between distal break points of the Prader-Willi/Angelman syndrome locus and was first described in association with MR and epilepsy. Together with recent studies that have also implicated this genomic imbalance in schizophrenia, our data indicate that this CNV shows considerable phenotypic variability. Further studies should aim to characterise the precise phenotypic range of this CNV and may lead to the discovery of genetic or environmental modifiers.

Figure 1

SNP data showing a microdeletion of 15q13.3. Log R ratios and B-allele frequencies are plotted against chromosome 15 position (b36). Visualised using Illumina Genome Viewer (v3.2.7), within BeadStudio. The red line shows a 1 M moving window average of the log R ratio. Hemizygosity in the mother and proband is shown by a drop in log R ratio (arrows) and missing heterozygote SNP calls (B-allele frequency ∼0.5).

Figure 2

Pedigree and aCGH data shown on CGH Analytics software (v3.4, Agilent). The green and red data points indicate probes with fluorescence ratios falling outside the software cutoff threshold of 0.25. The deleted regions are indicated by the vertical lines coloured according to the sample, analysed using a moving window average of 0.5 Mb. The plots are shown centred on probe A_14_P118326 (chr15: 29 482 614–29 482 671, b36 genome coordinates) shown by horizontal blue lines. The scale on the horizontal axes indicates relative copy number change. NA, DNA from this individual was not available.