Research

Participate in a Study

Simons Searchlight

If you or your child have a SETBP1-related disorder, please consider joining our registry to grow the size of the SETBP1 natural history and encourage research into this gene. It’s secure, private, and simple to sign up. Find out more about the SETBP1 Society registry through Simons Searchlight Read more.

RARE-X SETBP1 Data Collection Program

Share patient information in a set of short studies to help researchers identify a treatment and to learn about potential studies to help your child. Find out more about the SETBP1 Data Collection Program through RARE-X.

SETBP1 COMMUNITY RESEARCH STUDY (SCORES)

Tarleton State University and SETBP1 Society are partnering together for a community-based project to develop and drive research to meet the needs of the SETBP1 Community. The goals of this project are to identify and provide targeted resources to help parents of children with SETBP1 disorder and for parents’ responses to guide the direction of the research. Read more.

Boston Children’s Hospital – Fidelity

Boston Children’s Hospital launched a new study titled Fidelity that is focusing on several targeted disorders including SETBP1. For this project, they plan to CRISPR correct five samples from each targeted disorder to make these cells available for potential future research. This project will also involve developmental testing. The focus of the study is investigating the cellular basis of neurological disorders. Read more.

Chromosome 18 Registry and Research Society

The Chromosome 18 Registry and Research Society created and support the Chromosome 18 Clinical Research Center at UT Health San Antonio to advance research for those impacted by chromosome 18 genetic changes. They are another registry interested in collecting a natural history that encompasses the SETBP1 gene, and they have ongoing research projects that those with SETBP1 Disorder may participate in.

Doctors studying variants in SETBP1

Dr. Siddharth (Sid) Srivastava at Boston Children’s Hospital

Dr Sid is a pediatric neurologist at Boston Children’s Hospital specializing in neurogenetics. His research involves studying different genetic causes of neurodevelopmental presentations — such as autism, intellectual disability, cerebral palsy, and developmental regression — using the multimodal approach of gene discovery, cognitive/behavioral phenotyping, and biomarker identification. At Boston Children’s Hospital, he provides care to children in a variety of neurodevelopmental and neurogenetics clinics. He established a SETBP1 clinic and sees children with SETBP1-related disorders. Hear from Dr Sid talk about his connection with our SETBP1 community! If you would like to set up an appointment with Dr. Srivastava, you can send an email to Dr. Sid.

Dr. Bregje van Bon at Radboud Medical Center in Nijmegen, Netherlands

Dr. van Bon is a clinical geneticist with a specific interest in SETBP1 mutations. She is currently collecting research on individuals with SETBP1-related disorders at https://humandiseasegenes.nl/setbp1/. She combines clinical work in the hospital with teaching medical students and conducting research in the lab. She is currently seeing individuals with a SETBP1-related disorder. Dr van Bon also published the first phenotype paper for SETBP1 haploinsufficiency disorder titled Clinical delineation of SETBP1 haploinsufficiency disorder. Hear from Dr van Bon talk about his connection with our SETBP1 community! If you would like to set up an appointment with Dr. van Bon, you can send an email to Dr. van Bon.

Dr. Wendy Chung at Simon’s Searchlight

Dr. Chung’s team in New York is taking on the role of describing the clinical characteristics of individuals with SETBP1 variants. They have been enrolling SETBP1 families through the Simon’s Searchlight SETBP1 research registry to be able to learn more about SETBP1-HD. What genetic variants do individuals have in the SETBP1 gene? What are the most common features of SETBP1-HD? These questions are vital to understanding the scope and spectrum of the condition in order to help doctors, researchers, and families to better understand the impact and what to expect. Simon’s Searchlight also houses a SETBP1 biorepository of blood samples and iPSCs (induced pluripotent stem cells) from individuals with SETBP1-HD. Hear the latest Simons Searchlight update from Dr Wendy Chung.
To see Dr Wendy Chung in a clinical setting at Columbia University Medical Center, you can make an appointment by calling 212-305-5890.

Researchers studying variants in SETBP1

Prof. Simon E. Fisher at Max Planck Institute for Psycholinguistics in Nijmegen, Netherlands

Prof. Simon E. Fisher is the director of the Max Planck Institute for Psycholinguistics and Professor of Language and Genetics at the Donders Institute for Brain, Cognition and Behaviour in Nijmegen, the Netherlands. For one of his studies, his team is investigating the molecular biology of language-related genes, including SETBP1, and the proteins they encode, in order to uncover the functions of these proteins during normal brain development, and to reveal more about the molecular mechanisms underlying neurodevelopmental disorders. You can learn more about Prof. Simon E. Fisher at https://www.mpi.nl/people/fisher-simon.

Dr. Carl Ernst at McGill University in Montreal, Canada

Dr. Carl Ernst is an Associate Professor and the Canada Research Chair in Psychiatric Genetics at McGill University in the Departments of Psychiatry, Human Genetics, and the Integrated Program in Neuroscience. One of the projects in his lab focuses on the functional assessment of known neurodevelopmental disorders, including SETBP1, in patient-derived brain cells developed from skin, blood, or urine. This project aims to dissect the molecular pathways that lead from mutation to disease. You can learn more about Dr. Carl Ernst’s lab at http://mcgill.ca/psychiatricgenetics.

Dr. Angela Morgan at the University of Melbourne and Murdoch Childrens Research Institute

Dr. Angela Morgan is a professor at the University of Melbourne and Murdoch Children’s Research Institute with expertise in working with children with speech and language disorders associated with rare genetic conditions. She studies the impact SETBP1 loss of function has on speech and language, and can be reached at angela.morgan@mcri.edu.au. More information on the Translational Centre for Speech disordes at Murdoch Children’s Research Institute can be found at https://www.mcri.edu.au/research/strategic-collaborations/centres/nhmrc-cre-translational-centre-speech-disorders.

Dr. Vanessa Fear at the Telethon Kids Institute

Dr. Vanessa Fear has held a position with the Telethon Kids Institute, Genetic and Rare Diseases team as Senior Research Officer since 2018. Within this team her work focuses on application of CRISPR/Cas9 genome editing technology of pluripotent stem cells to assist with diagnoses of pediatric patients with genetic and rare diseases. More information on Telethon Kids Institute can be found at https://www.telethonkids.org.au/.

Researchers studying Animal Models

Audrey Brumback at the University of Texas at Austin

Audrey Brumback, M.D., Ph.D., is an assistant professor in the Department of Neurology and Department of Pediatrics and a board-certified pediatric neurologist in UT Health Austin Pediatric Neurosciences at Dell Children’s. Brumback is a physician scientist specializing in child neurology. Her research focuses on developing novel therapies for brain dysfunction based on modulation of neurophysiology. Brumback’s goal is to develop brain-circuit-based therapies for the developmental neuropsychiatric disorders she treats in her clinical practice. She currently has the SETBP1 indel mouse model to study how changes in the SETBP1 gene influence the activity of prefrontal cortex neurons. Understanding how prefrontal cortex neurons differ in their activity is an important step towards understanding why people with SETBP1-HD have so many challenges with executive functioning.

Rocco Piazza at University of Milano – Bicocca, Alessandro Sessa at San Raffaele Scientific Institute, Milan, and Luca Mologni at University of Milano – Bicocca

This team’s goal is to generate and to functionally validate a reversible knock-out mouse model for SETBP1 haploinsufficiency disorder (SETBP1-HD). The project will provide insightful information on the molecular consequences of the reactivation of SETBP1 protein in a knockout/haploinsufficient model that mimics SETBP1-HD. Our in vivo model will constitute a valuable platform to dissect the molecular mechanisms at the basis of the brain differences following SETBP1-HD and to study the effect of SETBP1 reactivation at different time-points during the life of the mouse model.

Maria Chahrour at the UT Southwestern Medical Center

Maria Chahrour is an assistant professor at the Eugene McDermott Center for Human Genetics and the departments of neuroscience and psychiatry at the University of Texas Southwestern Medical Center in Dallas, TX. Her team is currently investigating the cell-type specific role of SETBP1 in the brain and identifying its interactors.

Alexander Little at McMaster University and Maria Aristizabal at Queens University

Alexander Little is an assistant professor in the department of biology at McMaster University in Ontario, Canada. Maria Aristizabal is an assistant professor in molecular genetics at Queen’s University at Kingston. Professors Little and Aristizabal are currently characterizing SETBP1 LOF zebrafish and examining them for characteristics typical of SETBP1-HD patients to understand how these arise at the molecular levels.

Publications

SETBP1 haploinsufficiency (SETBP1-HD) publications
All SETBP1 publications

Research Models & Resources

SETBP1 KO Mouse Model

The Jackson Laboratory has currently developed a SETBP1 KO Cre/loxP Conditional mouse model and is maintaining a live colony. The Jackson Laboratory also developed and is maintaining a live colony of the SETBP1 98-nt frameshift deletion (indel) mouse model, as well. The characterization and mouse line availability for a SETBP1 KO Mouse tm1a Model are reported at the IMPC website.

SETBP1 IPSC Models and Blood Samples

Prof Simon Fisher at Max Planck Institute and Dr Carl Ernst at McGill University are currently developing induced pluripotent stem cells (IPSCs) with SETBP1 loss-of-function variants and SETBP1 gain-of-function variants. Prof Simon Fisher is also studying specific variants of uncertain significance. Simons Searchlight and Boston Children’s Hospital are storing blood samples of individuals with SETBP1 mutations and are currently developing induced pluripotent stem cells (IPSCs) as well. You can reach Simons Searchlight at https://www.sfari.org/resource/sfari-base/ and you can reach out to the Neuro Core regarding the blood samples and skin fibroblasts stored at Boston Children’s.

SETBP1 Official Patient Registry

SETBP1 Society has partnered with Simons Searchlight to collect, monitor, and maintain SETBP1 patient data for natural history collection and for promoting research and broadening our understanding of SETBP1 disorder. Learn about accessing the registry HERE!

Clinical Findings

Phenotype Papers
Phenotype Guide

SETBP1 haploinsufficiency (SETBP1-HD) Resource Guide
SETBP1 haploinsufficiency (SETBP1-HD) GeneReview for medical professionals

Phenotype Tracking

Dr Bregje van Bon, a clinical geneticist from Radboud University Medical Centre, is collecting patient data from individuals with SETBP1-HD and making those results available at Human Disease Genes website – SETBP1 disorder.

List of Known SETBP1 Mutations

The known pathogenic SETBP1 mutations can be viewed, downloaded, and updated HERE!
The suspected non-pathogenic SETBP1 mutations can be viewed and downloaded HERE!

Relevant Research & Resources in Rare Disorder Community

Information about re-purposing existing drugs for rare disease: Podcast, Article
Learn more about gene therapy from American Society for Gene & Cell Therapy: Article, Video
Information about the purpose of mouse models in rare disease research: Article
Learn more about comprehensive news and analysis of advances in autism research from Spectrum News: Website
SPARK — a landmark autism research project—aims to make important progress possible: Learn more
PubMed is a free research publications resource that is developed and maintained by the National Center for Biotechnology Information (NCBI), at the U.S. National Library of Medicine (NLM), located at the National Institutes of Health (NIH) Check it out