Hospital-wide research project aims to discover genetic causes of rare disease in children

Rare diseases are estimated to affect more than 30 million people in the United States, according to the Genetic and Rare Diseases Information Center at the National Institutes of Health. A transformational research project at Texas Children’s and Baylor seeks to identify the genetic causes of rare diseases. Scientists predict that about 13,000 genes cause disease in humans. About 8,000 remain unidentified.

The project, called TMC-CZI, is made possible by a two-year, $2.2 million grant from the Chan Zuckerberg Initiative. Rare disease is an area of focus for the initiative, which was established by Facebook (Meta) founder Mark Zuckerberg and his wife Priscilla Chan, MD.

“By studying rare diseases in children and understanding the physiologic role of genes and rare disease gene variants, not only can we develop strategies to help those patients, but we can increase our understanding of human physiology in general, said Katherine King, MD, PhD, Professor of Pediatrics in the Division of Infectious Diseases at Baylor College of Medicine, and a Co-Principal Investigator on the CZI grant. “This can lead to better therapies and treatments for diseases that affect the entire population.”

The project (https://www.hgsc.bcm.edu/czi) will enroll 200 study participants with rare, suspected genetic disorders and their parents. Patients with diseases affecting the heart, nervous system, reproductive organs and kidneys have been referred to the project so far.

Project components and principal investigators

1. Identifying patients with undefined suspected genetic syndromes
   Dr. King leads the project’s clinical coordination team, which makes Texas Children’s physicians aware of the opportunity to refer patients to the study and participate in follow-up research. Families receive a report of their sequencing data and free genetic counseling to help them understand the results. They also are connected to other patients with similar genetic syndromes.
2. Whole genome sequencing
   Genome sequencing is led by Richard Gibbs, PhD, Founder and Director of Baylor’s Human Genome Sequencing Center, which developed technology to accurately obtain the sequence and informatics tools to interpret the data. Dr. Gibbs is the Wofford Cain Chair and Professor of Molecular and Human Genetics at Baylor.
3. Characterizing effects of genetic mutations in animal models
   This work builds on the track record of Hugo Bellen, DVM, PhD, and his lab in discovering genes as the basis for diseases. Dr. Bellen’s team swaps gene variants in flies and studies the effects at the cellular, molecular and whole-body level. He is a Distinguished Service Professor in the Departments of Molecular and Human Genetics and Neuroscience at Baylor and the Neurogenetics Chair at Texas Children’s Duncan Neurological Research Institute.