These authors contributed equally to this work.
Fine mapping of Xq11.1-q21.33 and mutation screening of RPS6KA6, ZNF711, ACSL4, DLG3, and IL1RAPL2 for autism spectrum disorders (ASD)
Version of Record online: 22 FEB 2011
Copyright © 2011, International Society for Autism Research, Wiley-Liss, Inc.
Volume 4, Issue 3, pages 228–233, June 2011
How to Cite
Kantojärvi, K., Kotala, I., Rehnström, K., Ylisaukko-oja, T., Vanhala, R., von Wendt, T. N., von Wendt, L. and Järvelä, I. (2011), Fine mapping of Xq11.1-q21.33 and mutation screening of RPS6KA6, ZNF711, ACSL4, DLG3, and IL1RAPL2 for autism spectrum disorders (ASD). Autism Res, 4: 228–233. doi: 10.1002/aur.187
- Issue online: 6 JUN 2011
- Version of Record online: 22 FEB 2011
- Manuscript Accepted: 6 JAN 2011
- Manuscript Received: 27 JAN 2010
- Helsinki University Hospital Research Funding. Grant Number: ♯TYH7227
- The Academy of Finland Helsinki Finland
- The Medical Society of Finland, Helsinki, Finland
- Cure Autism Now
- European Union. Grant Number: ♯512158
- autism spectrum disorders;
- single nucleotide polymorphism;
About 80% of cases with autism express intellectual disability. Both in autism and in mental retardation without autism the majority of the cases are males, suggesting a X-chromosomal effect. In fact, some molecular evidence has been obtained for a common genetic background for autism spectrum disorders (ASD) and X-linked mental retardation (XLMR). In several genome-wide scans (GWS), evidence for linkage at X-chromosome has been reported including the GWS of Finnish ASD families with the highest multipoint lod score (MLS) of 2.75 obtained close to DXS7132 at Xq11.1. To further dissect the relationship between autism and genes implicated in XLMR, we have fine-mapped Xq11.1-q21.33 and analyzed five candidate genes in the region. We refined the region using 26 microsatellite markers and linkage analysis in 99 Finnish families with ASD. The most significant evidence for linkage was observed at DXS1225 on Xq21.1 with a nonparametric multipoint NPLall value of 3.43 (P = 0.0004). We sequenced the coding regions and splice sites of RPS6KA6 and ZNF711 residing at the peak region in 42 male patients from families contributing to the linkage. We also analyzed ACSL4 and DLG3, which have previously been known to cause XLMR and IL1RAPL2, a homologous gene for IL1RAPL1 that is mutated in autism and XLMR. A total of six novel and 11 known single nucleotide polymorphisms were identified. Further studies are warranted to analyze the candidate genes at Xq11.1-q21.33. Autism Res2011,4:228–233. © 2011 International Society for Autism Research, Wiley Periodicals, Inc.