Genetic Testing: The Cincinnati Undiagnosed and Rare Liver Disease Panel

Our panel offers a noninvasive yet comprehensive approach to genetic liver disease diagnosis. The identification of a genetic etiology plays a critical role in promoting early diagnosis and providing tailored medical management, thereby optimizing patient care.

The panel combines Exome Sequencing technology in conjunction with phenotype-driven analysis. It focuses on a curated list of 1,447 genes linked to hereditary liver diseases, which is the most comprehensive gene panel available for diagnosing genetic liver conditions as of 2024.

This approach allows for a comprehensive yet targeted analysis, unlike smaller panels that may miss important genes or whole exome sequencing that often leads to a vast number of variants in many genes, making it challenging to identify the actual disease-causing variants.

When uncertain genetic findings arise, our panel allows direct consultation with a physician. This enables discussions between the patient’s hepatologist and our experts to correlate findings with symptoms and other test results, helping determine if variants are disease-causing. Additionally, our research labs use cell and pre-clinical models to validate new genetic variants, ensuring greater diagnostic accuracy.

When to Consider Our Panel Testing

• Unexplained cholestasis
• Chronic hepatitis or cirrhosis of unknown cause
• Family history of unexplained liver disease

Basic, Clinical and Translational Research

Our commitment to translational research is showcased through various projects, such as:

• Zebrafish model of PFIC2 (BSEP deficiency): First-of-its-kind model for studying PFIC2, aiding disease mechanism understanding and treatment testing
• ABCC12 variant discovery: Identified a novel genetic cause of intrahepatic cholestasis, expanding our understanding of the disease
• Variant validation pipeline: Established a method to confirm the pathogenicity of newly discovered genetic variants using cell culture and pre-clinical models
• Stem cell and human tissue studies: Using patient-derived materials to investigate cellular causes of PFIC
• PFIC pre-clinical models: Developing and studying pre-clinical models to enhance understanding and test treatments
• Pharmacologic therapy development: Working on new drug therapies to improve liver function in PFIC patients
• Integrated PFIC research: Comprehensive approach combining in vitro studies, pre-clinical modeling, and clinical trials to develop new therapies

Outreach and Alliances

We are supported by generous donations from families who have lived with the impacts of rare and undiagnosed liver disease. This funding is crucial for sustaining our research initiatives and fostering collaborations that enhance our understanding and treatment of rare liver diseases.

How You Can Help

Supporting the Center for Undiagnosed and Rare Liver Diseases at Cincinnati Children’s can significantly impact the fight against PFIC and other rare liver diseases. Here are ways you can contribute:

Patient Registry - Registering as a patient can help advance research and improve treatment options for PFIC. This registry is crucial for collecting data that can lead to a better understanding and management of this rare disease.

Donations - Contributions are vital for sustaining research initiatives and enhancing care for children with rare liver diseases. Your donations directly support the development of new therapies and the establishment of dedicated clinics.

Connect with us for more information on patient registry and donations.