Current Research

ASXL Registry and Biobank 

The ASXL Registry, which is led by Dr. Bianca Russell at UCLA, counts the number of patients with Bohring-Opitz Syndrome (ASXL1), Shashi-Pena Syndrome (ASXL2), and Bainbridge-Ropers Syndrome (ASXL3) and gathers information about symptoms and complications over time. Study enrollment includes completing an initial questionnaire with opportunities to complete future questionnaires. Participants may also enroll in the biobank, which collects biological samples (typically blood) to be used in research studies. Further reading …

More information also at ARRE Foundation

Bohring-Opitz Syndrome EEG study 

A team from the University of California, Los Angeles led by Dr. Bianca Russell is launching a new research study looking at the neurologic function and brain wave activity (EEGs) in children with Bohring-Opitz Syndrome. Study enrollment includes an in-home EEG. To inquire about enrollment, please contact the UCLA study team at

Puberty Survey for all ASXL families 

We are currently working on a new survey regarding puberty in children with ASXL conditions. This study will be conducted through the ASXL Registry at UCLA and will be open to all ASXL1, ASXL2, and ASXL3 families. If you would like to participate, please enroll in our Registry and provide your genetic testing so you can receive the survey! If you are already enrolled in the Registry, you will automatically receive the puberty survey when it is available. Contact us at for more information regarding enrollment. 

Bianca E. Russell, M.D., FAAP, FACMG
Assistant Clinical Professor
Associate Program Director, Genetics Training Program
Division of Pediatric Genetics
Department of Pediatrics

Molecular and clinical biomarker development for Bohring-Opitz Syndrome

In 1990, humankind began a “voyage of discovery” unique in the history of the world. We explored inside the human body to discover more about ourselves. After 13 years, when the human genome was finally mapped, a whole new world of possibilities opened up.

ASXL1 is one of thousands of genes we found in that study that we still don’t understand, but we do know that when things go wrong with it, it can cause some very severe consequences. It can cause Bohring-Opitz Syndrome which in turn can lead to seizures, difficulty in speaking, walking, eating, and a laundry list of other problems.

Dr. Arboleda’s lab from UCLA is starting the journey to understand and, hopefully, treat the underlying causes of Bohring-Opitz Syndrome. She and her colleagues are studying the molecular mechanisms of the ASXL1 mutation and how it actually impacts cells. They are working with skin biopsies to find differences in DNA or chemicals for people with BOS so that they have a way to test if certain drugs make a difference in those biomarkers. Dr. Arboleda’s project helps lay a foundation for the discovery of drugs that could open up a new beautiful world of better health for affected children.

More information: ARRE Foundation

Establishment of stem cell models and enteric nervous system screening platforms for ASXL disorders

Using the cutting edge techniques of Pluripotent Stem cell research Dr. Drukker is paving the way to discovering why children with ASXL disorders have such a hard time holding down a meal. This is no small problem. One of the common secondary diagnoses for these kids is failure to thrive and “stomach migraines” that cause severe vomiting, pain and suffering in these little ones. Most of them have been hospitalized for these reasons and some multiple times over and over again. The worst part is that doctors just can’t seem to figure out what is going on, and none of the medicines that have been tried seem to help.

Dr. Drukker is working to change all that. In his new state-of-the-art lab he is turning cells from patient skin biopsies into a working model of their digestive system. Then using robots he can test hundreds of medications and closely monitor the reaction of these very unique “mini-stomachs” to all of them. All without patient side effects or danger. 

Eating should be something that people look forward to, but so many kids with ASXL disorders have had that pleasure turned to pain. We are thrilled to watch and see if Dr. Drukker can turn that around.

More information: ARRE Foundation

Development and diagnostic applications of ASXL1 and ASXL3 DNA methylation signatures

Epigenetics is the new buzzword of science. It literally means “above the genes” and has to do with the way those genes are expressed. Some genes are thought to be “epigenetic regulators” that put down markers, like bookmarks, that help the body decide which gene instructions to use. That’s how your body creates eye cells that are completely different from your muscle cells from the same “book” of DNA. Recent studies make us think ASXL genes may be some of these “epigenetic regulators.”

Dr. Weksberg and her team from Sick Kids Toronto want to discover more. They have already looked at about 25 similar genes and found a specific pattern or “signature” to each. They hope that their research into ASXL1 and ASXL3 signatures will lead to a better understanding of what these genes actually do in the body and how they do it. Answers in this area will have far-reaching effects for all of genetics and even cancer studies. But, of course, for children and families affected, the most important thing is that it will bring us one step closer to safe and effective treatments for the children who suffer — and that’s something to get excited about.

More information: ARRE Foundation

Identifying molecular targets for ASXL1 alteration-associated BOS

Imagine being one in a hundred million, literally. Imagine having a rare syndrome that no one understands. Then you meet your mice. Mice that have been developed to study your syndrome and that may help to better your life. This is what happened to one little girl’s family in Florida. Her name is Hazel and she has ASXL1/Bohring-Opitz Syndrome (BOS).

Dr. Yang and her colleagues from the University of Texas developed these mice a few years ago and have already made some exciting discoveries about how the ASXL gene works. The mice develop with a lot of the same symptoms that Hazel and her “BOS siblings” have. The hope is that with more study of these mice we can come to understand the “why” behind the syndrome, and that “why” is the first step to a big “what” – “what” we can do to help Hazel live a better life. And that’s even more exciting than meeting a mouse just like you.

More information: ARRE Foundation

The role of Asxls in Bohring-Opitz-Syndrome

Public Abstract

PhD student: Friederike Matheus
Project leader and group leader: Dr. Micha Drukker
Group of Human Pluripotent Stem Cell Differentiation
Helmholtz Zentrum Muenchen

Up until 2013, only mutations in the Asxl1 gene have been linked to Bohring-Opitz Syndrome (BOS). These mutations code for dysfunctional ASXL1 proteins (1, 2). Recently, mutations in an additional member of the Asxl gene family, Asxl3, has been associated with cases of BOS-like syndrome (3).  Since BOS is a congenital disease that exhibits a broad spectrum of defects, we hypothesized that the ASXL proteins, probably together with other factors, play a crucial role in the very first stages of life. Therefore, to shed light on BOS, we work on discovering the functions of ASXLs in normal human development and in models of BOS. It occurred to us that the ideal model for BOS would be one that is based on human pluripotent stem cells that are generated by reprogramming of patient skin cells. The reprogramming process produces human embryonic-like cells, known as induced pluripotent stem cells (iPS cells), which can be differentiated in tissue culture for imitating human embryonic and fetal development. Such iPS cells and differentiation protocols can be used as a system to study the mechanisms of BOS.

To achieve these goals we make use of state-of-the-art molecular biology techniques for reprogramming. We begin with very small skin biopsies from BOS patients, producing patient specific iPS cell lines within several weeks. Then we analyze molecular pathways that are perturbed by the mutations in Asxl1 during differentiation of patient iPS cells. We investigate genetic and epigenetic pathways; this means that we analyze how Asxls control gene expression of embryonic genes, and how mutations in Asxls disrupt control of gene expression and protein function. Our prospect for this project is that it will shed light into what is “going wrong” in the developmental progress of BOS patients, and we hope that this knowledgebase in turn will allow us to develop therapies for BOS. Since so little is known about the mechanisms that underlie BOS, we feel that basic studies of BOS on the cellular level are necessary for therapeutic breakthroughs.

Our research group is located in the Helmholtz Center Munich, and we are deeply interested in broadening our patient sample panel, and in information about patients that can assist us in understudying BOS. Therefore we would be thankful for communications with families as well as physicians and geneticists.

Update October 2018: Friederike Matheus has published her study. Read here her results of “The role of Additional sex combs – like genes in human pluripotent stem cell differentiation and congenital disorders”

Please don’t hesitate to contact: Friederike Matheus

Print The role of Asxls in Bohring-Opitz-Syndrome – Public Abstract BOS-Text MD-Helmholtz Center Munich.