Bohring-Opitz syndrome is characterized by severe intellectual disability, distinctive facial features and multiple congenital malformations. We sequenced the exomes of three individuals with Bohring-Opitz syndrome and in each identified heterozygous de novo nonsense mutations in ASXL1, which is required for maintenance of both activation and silencing of Hox genes. In total, 7 out of 13 subjects with a Bohring-Opitz phenotype had de novo ASXL1 mutations, suggesting that the syndrome is genetically heterogeneous.
Subscribe to Journal
Get full journal access for 1 year
only $18.75 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Oberklaid, F. & Danks, D.M. Am. J. Dis. Child. 129, 1348–1349 (1975).
Hastings, R., Cobben, J.M. & Gillessen-Kaesbach, G. et al. Eur. J. Hum. Genet. 19, 513–519 (2011).
Bohring, A., Oudesluijs, G.G., Grange, D.K., Zampino, G. & Thierry, P. Am. J. Med. Genet. A. 140, 1257–1263 (2006).
Ng, S.B. et al. Nat. Genet. 42, 790–793 (2010).
Gilissen, C. et al. Am. J. Hum. Genet. 87, 418–423 (2010).
Hoischen, A. et al. Nat. Genet. 42, 483–485 (2010).
Kaname, T. et al. Am. J. Hum. Genet. 81, 835–841 (2007).
Bisgaard, A.M. et al. Eur. J. Med. Genet. 50, 243–255 (2007).
Fisher, C.L. et al. Dev. Biol. 337, 9–15 (2010).
Kleefstra, T., Nillesen, W.M. & Yntema, H.G. GeneReviews (eds Pagon, R.A., Bird, T.D., Dolan, C.R. & Stephens, K.) (University of Washington, Seattle, Washington, USA, 1993–2010 ).
Gelsi-Boyer, V. et al. Br. J. Haematol. 151, 365–375 (2010).
Boultwood, J. et al. Leukemia 24, 1062–1065 (2010).
Bench, A.J. et al. Oncogene 19, 3902–3913 (2000).
Rodríguez-Santiago, B. et al. Am. J. Hum. Genet. 87, 129–138 (2010).
We thank the subjects and their parents for participation in this study. We thank P. Arts, M. Steehouwer and personnel from the Microarray Facility and Sequencing Facility Nijmegen for technical assistance. We thank N. Wieskamp, J. de Ligt and M. Rosario for bioinformatics support in data analysis. The authors are grateful to M. Sipponen and J. Ignatius for collaborative efforts relating to patient 4 and to C. Fisher for information on the Asxl1 knockout mouse. This study was financially supported by the Netherlands Organization for Health Research and Development (ZonMW grants 917-66-36 and 911-08-025 to J.A.V., 916-86-016 to L.E.L.M.V. and 917-86-319 to B.B.B.A.d.V.), the EU-funded TECHGENE project (Health-F5-2009-223143 to J.A.V.) and the AnEUploidy project (LSHG-CT-2006-37627 to A.H., B.W.M.v.B., H.G.B., B.B.B.A.d.V. and J.A.V.). The Family Federation of Finland is funded by Finland's Slot Machine Association (RAY). B. R.-S. was supported by a postdoctoral fellowship of the Fondo Investigación Sanitaria, Spain (FIS CD06/00019).
The authors declare no competing financial interests.
About this article
Cite this article
Hoischen, A., van Bon, B., Rodríguez-Santiago, B. et al. De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome. Nat Genet 43, 729–731 (2011). https://doi.org/10.1038/ng.868
Bainbridge-ropers syndrome caused by loss-of-function variants in ASXL3: Clinical abnormalities, medical imaging features, and gene variation in infancy of case report
BMC Pediatrics (2020)
Exome sequencing reveals a novel splice site variant in HUWE1 gene in patients with suspected Say-Meyer syndrome
European Journal of Medical Genetics (2020)
Molecular Case Studies (2020)
Extending the phenotypic spectrum of Bohring‐Opitz syndrome: Mild case confirmed by functional studies
American Journal of Medical Genetics Part A (2020)
Perithyroidal Salivary Gland Acinic Cell Carcinoma: Morphological and Molecular Attributes of a Unique Lesion
Head and Neck Pathology (2020)