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A small recurrent deletion within 15q13.3 is associated with a range of neurodevelopmental phenotypes

Abstract

We report a recurrent 680-kb deletion within chromosome 15q13.3 in ten individuals, from four unrelated families, with neurodevelopmental phenotypes including developmental delay, mental retardation and seizures. This deletion likely resulted from nonallelic homologous recombination between low-copy repeats on the normal and inverted region of chromosome 15q13.3. Although this deletion also affects OTUD7A, accumulated data suggest that haploinsufficiency of CHRNA7 is causative for the majority of neurodevelopmental phenotypes in the 15q13.3 microdeletion syndrome.

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Figure 1: Results of array CGH analysis with a 15q13.3 region-specific high-resolution 135K oligonucleotide microarray (NimbleGen).

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References

  1. Sharp, A.J. et al. Nat. Genet. 40, 322–328 (2008).

    Article  CAS  Google Scholar 

  2. Miller, D.T. et al. J. Med. Genet. 46, 242–248 (2009).

    Article  CAS  Google Scholar 

  3. Ben-Shachar, S. et al. J. Med. Genet. 46, 382–388 (2009).

    Article  CAS  Google Scholar 

  4. van Bon, B.W. et al. J. Med. Genet. 46, 511–523 (2009).

    Article  CAS  Google Scholar 

  5. Stefansson, H. et al. Nature 455, 232–236 (2008).

    Article  CAS  Google Scholar 

  6. International Schizophrenia Consortium. Nature 455, 237–241 (2008).

  7. Helbig, I. et al. Nat. Genet. 41, 160–162 (2009).

    Article  CAS  Google Scholar 

  8. Dibbens, L.M. et al. Hum. Mol. Genet. 18, 3626–3631 (2009).

    Article  CAS  Google Scholar 

  9. Taske, N.L. et al. Epilepsy Res. 49, 157–172 (2002).

    Article  CAS  Google Scholar 

  10. Leonard, S. & Freedman, R. Biol. Psychiatry 60, 115–122 (2006).

    Article  CAS  Google Scholar 

  11. Stephens, S.H. et al. Schizophr. Res. 109, 102–112 (2009).

    Article  Google Scholar 

  12. Lu, X. et al. PLoS One 2, e327 (2007).

    Article  Google Scholar 

  13. Makoff, A.J. & Flomen, R.H. Genome Biol. 8, R114 (2007).

    Article  Google Scholar 

  14. Kayagaki, N. et al. Science 318, 1628–1632 (2007).

    Article  CAS  Google Scholar 

  15. Broide, R.S. et al. Mol. Pharmacol. 61, 695–705 (2002).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank all families who participated in this study; C. Carvalho, W. Gu, J.R. Lupski, C. Shaw and M. Strivens for helpful discussion; and P. Eng, Z. Ou and M. Suzuki for technical assistance. A.L.B. was supported by US National Institutes of Health grants HD-037283, M01-RR00188 (General Clinical Research Center), HD-024064 (Mental Retardation and Developmental Disabilities Research Center) and RR-019478 (Rare Disease Clinical Research Consortia) and by generous support from the William Stamps Farish Fund. P.S. was supported in part by grant R13-0005-04/2008 from the Polish Ministry of Science and Higher Education.

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B.L., H.S.H. and L.L.I. provided clinical information. M.S., C.P.S., S.N., G.S.P., C.N.-S. and A.L.B. coordinated clinical data collection. M.S., S.S.B., S.N., C.N.-S., Z.X., J.R.G. and P.S. performed array CGH, DNA sequencing and bioinformatic analyses. M.S., C.P.S., A.P., S.W.C., A.L.B. and P.S. interpreted the data, performed critical revisions and wrote the manuscript. M.S., C.P.S., A.L.B. and P.S. oversaw manuscript preparation and revision.

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Correspondence to Arthur L Beaudet.

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M.S., C.P.S., S.S.B., Z.X., A.P., S.W.C., J.R.G., A.L.B. and P.S.[AU: Our policy is to list authors mentioned here individually, with initials; please check that this list is complete.] are based in the Department of Molecular and Human Genetics at Baylor College of Medicine (BCM), which offers extensive genetic laboratory testing, including use of arrays for genomic copy number analysis, and derives revenue from this activity.

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Shinawi, M., Schaaf, C., Bhatt, S. et al. A small recurrent deletion within 15q13.3 is associated with a range of neurodevelopmental phenotypes. Nat Genet 41, 1269–1271 (2009). https://doi.org/10.1038/ng.481

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