ASXL-Related Disorders Natural History Study and Biobank

This study has been designed to serve as a collaborative hub for ASXL research projects. It is multi-site hosted at the University of California Los Angeles (UCLA) under the direction of clinical geneticist Bianca Russell, MD with collaboration from other researchers around the world. Collaborating sites include Kennedy Krieger Institute, Boston Children’s Hospital, Cincinnati Children’s Hospital, and Duke University.

The study includes the collection of participant data through core surveys that are part of the Natural History Study. Additionally, other researchers can use the study’s infrastructure to ask specific research questions through surveys or other data collection methods. Study data and samples can be shared with other researchers upon request (see “Who can access participant data” below for more information).

As a participant, this means that you only need to enroll in this study once, and then you will receive additional opportunities to take surveys or provide clinical information that may provide new insights into your or your child’s condition.

The eligibility criteria for this study includes:

• Diagnosis of an ASXL-related disorder (Bohring-Opitz Syndrome, Shashi-Pena Syndrome, or Bainbridge-Ropers Syndrome) through genetic testing that identifies a genetic change in the ASXL1, ASXL2, or ASXL3 gene*
• Any age
• Any geographic location
• Some written and spoken language limitations apply (see below)

*All genetic testing is reviewed by the study tea to determine eligibility.

Language limitations: This study includes several data collection opportunities, including surveys and questionnaires. Some surveys are available in multiple languages and others are only available in English. The Research Coordinate can answer questions about the availability of specific data collection opportunities in specific languages.

If you are interested in participating in this study, the first step is to complete the enrollment process. This includes review of your genetic report for eligibility and providing informed consent to participate. Enrollment steps are as follows:

1. Complete the online enrollment intake form
2. A member of the research team at UCLA will get back to you (typically within 2-3 business days) to coordinate you sending your or your child’s genetic report via secure email for review by the clinical research team
3. If your or your child’s genetic report indicates eligibility for the study, the Research Coordinator will reach out to schedule a 15-20 minute virtual meeting to review information about the study and answer your questions
4. Complete and sign the informed consent agreement which is sent via email to be signed digitally (DocuSign)

If you have additional questions or would like to check your child’s enrollment status, please contact the Research Coordinator at asxl-chromatin-registry@mednet.ucla.edu.

Once you are enrolled in the ASXL-Related Disorders Natural History Study, you can participate in other specific surveys or data collection efforts conducted through the study for which you or your child meet the eligibility criteria. Participation steps include:

1. Upon enrollment, complete the initial health survey
2. Complete any other surveys you or your child are eligible to participate in
3. Watch for new surveys or data collection opportunities (announced by email and shared by the ARRE Foundation)

If you are interested in providing an optional biological sample (typically blood), the Research Coordinator will discuss this with you during your enrollment call or you can reach out to the Research Coordinator after enrollment.  At this time, sample collection is primarily limited to the United States due to logistical challenges but samples from other countries may be accepted on a case-by-case basis.

If the research team is interested in collecting a blood sample from your family, the Research Coordinator will work with you to coordinate collection. This may include:

1. Sending you a collection kit that you can take to a scheduled laboratory appointment and mail back to UCLA with a prepaid label
2. Scheduling a blood draw in clinic if you are local to the Los Angeles area

The ASXL-Related Disorders Natural History Study and Biobank is designed to support:

• Describing the clinical features of ASXL-related disorders, their prevalence, and what these features may look like over time
• Providing further insight into clinical management of ASXL-related disorders, including providing evidence for new screening recommendations
• Supporting the development of clinical endpoints for future clinical trials
• Providing supporting evidence for more accurate genetic diagnoses of these conditions
• Providing biological samples directly from affected individuals, which are valuable research tools in the development of treatments

Results from the ASXL-Related Disorders Natural History Study and Biobank are shared regularly with the ASXL community in several different ways. These include:

• Digital newsletter sent to participants twice per year
• Participation in the ASXL-Related Disorders Natural History Study Steering Committee, which is open to the community twice per year (dates and registration information is shared by the ARRE Foundation)
• Webinars and online events hosted by the ARRE Foundation
• Presentations at clinical and scientific meetings
• Research publications

Past publications from this study can be found here.

This study is primarily funded by the ARRE Foundation. Previous financial support was provided by the Bohring-Opitz Syndrome Foundation.

Access to de-identified data and samples from the study is governed by the ASXL-Related Disorders Natural History Study Steering Committee, which includes doctors, researchers, and three ASXL parents (each representing the ASXL1, ASXL2, and ASXL3 family communities). The parent members of the committee are nominated by the ARRE Foundation. Researchers requesting data or samples from the study submit a formal request which is evaluated and voted on by the steering committee. All data and samples requested by nonprofit academic researchers are provided free of charge (less any shipping or material costs).

This study is led by Dr. Bianca Russell, a clinical geneticist at UCLA, and her research team. If you have questions about this study, please contact the Research Coordinator at asxl-chromatin-registry@mednet.ucla.edu.