De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome.

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.

• Authors: Alexander Hoischen, 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
• Journal: Nature genetics (Nat Genet) Vol. 43 Issue 8 Pg. 729-31 (Jun 26 2011) ISSN: 1546-1718 [Electronic] United States
• PMID: 21706002 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ASXL1 protein, human
• Codon, Nonsense
• Repressor Proteins

Topics

• Codon, Nonsense (genetics)
• Craniosynostoses (etiology, pathology)
• Face (abnormalities, pathology)
• Humans
• Intellectual Disability (etiology, genetics, pathology)
• Polymorphism, Single Nucleotide (genetics)
• Repressor Proteins (genetics)