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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Sharp, A.J. et al. Nat. Genet. 40, 322–328 (2008).
Miller, D.T. et al. J. Med. Genet. 46, 242–248 (2009).
Ben-Shachar, S. et al. J. Med. Genet. 46, 382–388 (2009).
van Bon, B.W. et al. J. Med. Genet. 46, 511–523 (2009).
Stefansson, H. et al. Nature 455, 232–236 (2008).
International Schizophrenia Consortium. Nature 455, 237–241 (2008).
Helbig, I. et al. Nat. Genet. 41, 160–162 (2009).
Dibbens, L.M. et al. Hum. Mol. Genet. 18, 3626–3631 (2009).
Taske, N.L. et al. Epilepsy Res. 49, 157–172 (2002).
Leonard, S. & Freedman, R. Biol. Psychiatry 60, 115–122 (2006).
Stephens, S.H. et al. Schizophr. Res. 109, 102–112 (2009).
Lu, X. et al. PLoS One 2, e327 (2007).
Makoff, A.J. & Flomen, R.H. Genome Biol. 8, R114 (2007).
Kayagaki, N. et al. Science 318, 1628–1632 (2007).
Broide, R.S. et al. Mol. Pharmacol. 61, 695–705 (2002).
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.
Author information
Authors and Affiliations
Contributions
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.
Corresponding author
Ethics declarations
Competing interests
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.
Supplementary information
Supplementary Text and Figures
Supplementary Note, Supplementary Tables 1 and 2 and Supplementary Figures 1 and 2. (PDF 448 kb)
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ng.481
This article is cited by
-
The OTUD7A-Ankyrin pathway: a newly identified disease mechanism for the 15q13.3 microdeletion disorder
Molecular Psychiatry (2023)
-
Impaired OTUD7A-dependent Ankyrin regulation mediates neuronal dysfunction in mouse and human models of the 15q13.3 microdeletion syndrome
Molecular Psychiatry (2023)
-
First report of two successive deletions on chromosome 15q13 cytogenetic bands in a boy and girl: additional data to 15q13.3 syndrome with a report of high IQ patient
Molecular Cytogenetics (2019)
-
Interactive effects between hemizygous 15q13.3 microdeletion and peripubertal stress on adult behavioral functions
Neuropsychopharmacology (2019)
-
Association study and mutation sequencing of genes on chromosome 15q11-q13 identified GABRG3 as a susceptibility gene for autism in Chinese Han population
Translational Psychiatry (2018)