One Cause of BOS: Novo mutation ASXL1

Prior to 2011, geneticists relied on making a clinical diagnosis by recognizing the distinguishable physical characteristics in the appearance of their patients. In 2011, researchers at the Radboud University Nijmegen medical centre used “next generation sequencing” to find the genetic cause of Bohring-Opitz Syndrome. Since then it has been possible to confirm the BOS diagnosis with a genetic DNA test. They found that 7 of 13 examined patients with the BOS phenotype had the mutation in the ASXL1 gene.
The final results of the research carried out at Radboud University Nijmegen medical centre:

1. A novo mutation of the ASXL1 gene causes BOS
2. BOS is genetically heterogeneous (miscellaneous), meaning there must be at least one other cause of BOS.

Because another 6 children with clinical diagnosis of BOS didn’t have this mutation, this indicates that other genes may be involved in this syndrome (Radboud UMC[3], Hoischen et al. 2011) or  that a somatic mosaicism should be considered as cause in patients with a typical phenotype and no detectable mutation. (Russell et al. 2015)

The ASXL1 gene

The ASXL1 gene (OMIM 605039) is located on the chromosome 20q11.21.


The ASXL1 gene plays an important role in activating and deactivating HOX genes. These HOX genes are essential for the development of fertilized ovum to adult organism.

It can increase the production of some proteins and decrease the production of others. Because the protein is involved in controlling the expression of many other genes the syndrome can cause changes in many different parts of the body. [4]

The ASXL1 gene is already known to geneticists: a link with cancer has been established. There are two possible situations:

1. The novo ASXL1 mutation: this causes Bohring-Opitz Syndrome. The gene mutates at conception, creating a developmental disorder that leads to Bohring-Opitz Syndrome.
2. The somatic ASXL1 mutation: The mutation occurs during later life. The patient has an increased risk of acute myeloid leukaemia, a form of blood cancer (AML).[5]

[3] 4 November 2015

[4]Unique (Understanding Chromosome Disorders) : Bohring-Opitz Syndrome. Leaflet by Dr Joanna Kennedy, Academic Paediatric Trainee, Severn Deanery and reviewed by Professor Ruth Newbury – Ecob, MB ChB, MD, FRCP, FRCPCH, Consultant Clinical Geneticist, Department of Clinical Genetics, University Hospitals Bristol NHS Foundation Trust. Unique 2017.

[5]  4 November 2015