De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome

  • Nat Genet. 2011 Jun 26;43(8):729-31. doi: 10.1038/ng.868.
Alexander Hoischen  1 ,  Bregje W M van Bon ,  Benjamín Rodríguez-Santiago ,  Christian Gilissen ,  Lisenka E L M Vissers ,  Petra de Vries ,  Irene Janssen ,  Bart van Lier ,  Rob Hastings ,  Sarah F Smithson ,  Ruth Newbury-Ecob ,  Susanne Kjaergaard ,  Judith Goodship ,  Ruth McGowan ,  Deborah Bartholdi ,  Anita Rauch ,  Maarit Peippo ,  Jan M Cobben ,  Dagmar Wieczorek ,  Gabriele Gillessen-Kaesbach ,  Joris A Veltman ,  Han G Brunner ,  Bert B B A de Vries
Affiliations
  • 1. Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
PMID: 21706002 DOI: 10.1038/ng.868
Abstract

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.