De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome

• Published in: Nature genetics Vol. 43; no. 8; pp. 729 - 731
• Main Authors: Hoischen, Alexander, van Bon, Bregje W M, Rodríguez-Santiago, Benjamín, Gilissen, Christian, Vissers, Lisenka E L M, de Vries, Petra, Janssen, Irene, van Lier, Bart, Hastings, Rob, Smithson, Sarah F, Newbury-Ecob, Ruth, Kjaergaard, Susanne, Goodship, Judith, McGowan, Ruth, Bartholdi, Deborah, Rauch, Anita, Peippo, Maarit, Cobben, Jan M, Wieczorek, Dagmar, Gillessen-Kaesbach, Gabriele, Veltman, Joris A, Brunner, Han G, de Vries, Bert B B A
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2011; Nature Publishing Group
• Subjects: 631/208/2489/144; Agriculture; Animal Genetics and Genomics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; brief-communication; Cancer; Cancer Research; Codon, Nonsense - genetics; Complex syndromes; Congenital defects; Craniosynostoses - etiology; Craniosynostoses - pathology; Diagnosis; Experiments; Face - abnormalities; Face - pathology; Fundamental and applied biological sciences. Psychology; Gaming machines; Gene Function; Genes; Genetic aspects; Genetics of eukaryotes. Biological and molecular evolution; Genotype & phenotype; Human Genetics; Humans; Intellectual Disability - etiology; Intellectual Disability - genetics; Intellectual Disability - pathology; Medical genetics; Medical research; Medical sciences; Mutation; Opitz syndrome; Physiological aspects; Polymorphism, Single Nucleotide - genetics; Repressor Proteins - genetics; Suppression, Genetic; Switzerland; Nonsense mutation; De novo; Syndrome
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.868

Han Brunner and colleagues report the identification of de novo nonsense mutations in ASXL1 in individuals with Bohring-Opitz syndrome, which is characterized by intellectual disability, distinctive facial features and multiple congenital malformations. 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.