UAB HRFD Core Center: Core A: The Hepato/Renal Fibrocystic Diseases Translational Resource

In 2005, The University of Alabama at Birmingham established a NIDDK-funded, interdisciplinary center of excellence in PKD-related research, with specific emphasis on recessive PKD. In the previous Core Center award period, we developed a Core Resource to capture clinical and mutational data for ARPKD patients ("Core A: ARPKD Clinical and Genetic Resource", NCT00575705). However, studies in the last several years have demonstrated that ARPKD and other single gene disorders characterized by renal cystic disease and extra-renal phenotypes share numerous pathogenic features. In the current competitively- renewed Center, we have expanded this Core resource to include other hepato/renal fibrocystic diseases.

Goals for the Core A: The Hepato/Renal Fibrocystic Diseases Translational Resource are:

1. - Clinical Database:

   • Expand our comprehensive Clinical Database to include information from all patients who meet the inclusion criteria for hepato/renal fibrocystic diseases.

2. - Mutational Database:

   • Test children with ARPKD and other hepato/renal fibrocystic disease to identify genetic mutations, establish a DNA bank for patients with hepato/renal fibrocystic diseases and develop a Mutational Database. This Database will be capable of linking clinical and mutational information via a unique identifier in a searchable format to facilitate genetic research (e.g. genotype-phenotype correlations, new disease gene studies, and modifier gene studies), translational studies, and clinical trials.

     3- Tissue Resource:

   • Much of the research that is performed on diseases of the kidney, including recessive genetic diseases, requires human tissue from both affected as well as non-affected (controls) individuals. In this Core Resource, we are establishing an independent tissue resource which would supply investigators throughout North America with samples of hepato/renal fibrocystic disease affected tissues for studies of these disorders.

     4- Educational Resource:

   • Expand our multi-media, web-based resource to provide a reliable up-to-date, and comprehensive informational resource for ARPKD and Hepato/Renal Diseases families, their physicians, and genetic counselors.

All the information regarding participation in "Core A: The Hepato/Renal Fibrocystic Diseases Translational Resource" is available at: http://www.arpkdstudies.uab.edu/.

The entry portal for Core A is designed so that physicians who contact the CLIA-certified UAB Medical Genomics Laboratory (MGL) requesting information about PKHD1 testing and any patient/parent/legally authorized representative looking for information online about any of the hepato-renal diseases included in this study will be directed to the UAB Hepato/Renal Fibrocystic Disease Translational Resource website http://www.arpkdstudies.uab.edu/.

The Informed Consent for the Clinical Database and Information for the participant will be posted on the website (http://www.arpkdstudies.uab.edu/) for review by potential participants and follow-up discussions with the PI and/or Research Nurse Coordinator. In addition, materials in paper format can be sent to interested potential participants upon request.

Two key elements will be required for patient enrollment: 1) certification that informed consent has been obtained, and 2) participant and physician contact information form completed by the participant.

The UAB release of information form, information for the physician and instructions on how to enter data will be posted in the website available to the physician.

This study does not provide free genetic testing. Clinical genetic testing is available via UAB Medical Genomics Laboratory (CLIA and CAP approved) as a fee-for-service. In special cases (eg. presenting at an older age, mainly with liver or pancreatic disease) contact Dr. Guay-Woodford at lgw@uab.edu.

Once receipt of the requisite items is confirmed, the following actions will proceed:

1. Each participant will be assigned a unique code identifier in the database and a clinician-specific web field will be opened for the participant identifier.
2. The participant/parents will confirm the name of their clinician to the database and notify their physician and/or genetic counselor (clinicians) of their intent to participate in this study.
3. The clinician will access the Physician Link on the website and follow the instructions about how to post data to the website. Once this is done, the name of the patient will be deleted from the online database and only the unique identifier will be used. Each clinician permitted to access this website will be tracked with a login procedure that includes a process to verify who is entering the system. Clinical data will be provided by the participant's physician through the web-based entry system, coded with a unique identifier, and entered into the secure Clinical Database as an initial visit data (F01 or primary data form) and annual follow up (F11 or follow up form). Data entry will last the duration of this study. No names or initials will be collected on these data forms, but gender and date of birth (which will be converted to age and only the month and year will be kept on file) will be requested. The physician will not receive a monetary incentive for entering data.
4. Blood samples for diagnostic testing (with signed clinical genetic testing consent) will be sent to the UAB MGL. The UAB MGL will perform standardized fee for service testing for PKHD1 mutations. The clinical result will be reported to the patient's physician/genetic counselor. As needed, genetic counseling services can be made available through the UAB Department of Genetics (fee for service).
5. Blood samples for research purposes will come directly to the research lab from patients/families signing the study consent and agreeing to have DNA extraction/EBV transformation/or both. Adult and children participants need two tsp of blood and infants need one tsp of blood.
6. This study does not provide free genetic testing. Clinical genetic testing is available via UAB Medical Genomics Laboratory (CLIA and CAP approved) as a fee-for-service. The result of the genetic testing will be entered into the Mutational Database if the participant or their representative provides consent to participate in the Database.
7. Our center can be notified directly by a local physician authorized by the patient or the patient can contact our center directly to donate hepato/renal fibrocystic disease tissue. The research coordinator will contact the possible participant/parent/legally authorized representative to discuss the study and their willingness to participate in this research. If the study consents are signed, the research coordinator will call the center/pathologist, sending the sample and provide them with instructions on how to prepare and ship sample. On arrival to Dr. Guay-Woodford's lab, the sample will be de-identified and coded with the participant's unique identifier and transported to the UAB Tissue Collection and Banking Facility.

In view of the genetics and demographics of the recessive disorders comprising the spectrum of hepato/renal fibrocystic diseases, we estimate that 50% of the subjects will be female; that 90% of the subjects will be Caucasian and the remainder will belong to the following racial/ethnic categories: 5% African-Americans; 3% Hispanics; 1% Asians; and 1% or less will be other categories.

• Hepato/Renal Fibrocystic Disease
• Autosomal Recessive Polycystic Kidney Disease
• Joubert Syndrome
• Bardet Biedl Syndrome
• Meckel-Gruber Syndrome
• Congenital Hepatic Fibrosis
• Caroli Syndrome
• Oro-Facial-Digital Syndrome Type I
• Nephronophthisis
• Glomerulocystic Kidney Disease

Inclusion Criteria:

• Demonstration of hepato/renal fibrocystic disease by clinical information, imaging studies, biopsy, autopsy, or genetic testing.

Exclusion Criteria:

• ADPKD Urinary tract malformations Major congenital anomalies of other systems