GENETICS AND FSGS
Focal Segmental GlomeruloSclerosis (FSGS) is a disorder in the blood-filtering parts of the kidney called the glomeruli. Focal and segmental refer to the pattern of damage to the glomerulus and glomerulosclerosis refers to the damage or scarring (sclerosis) of the glomerulus. Specifically, focal refers to patches within the kidney that are affected and segmental indicates that only a portion of the glomerulus is affected. FSGS damages the glomerulus and allows protein to leak into the urine (proteinuria) resulting in swelling and a group of clinical changes called nephrotic syndrome. Over time, the damage to the kidney may cause kidney failure. FSGS is only one of many causes of kidney failure or end-stage renal disease (ESRD). In the last 25 years, we have identified over 150 families from all over the world with two or more family members with FSGS. This is considered familial or hereditary FSGS.
We are using multiple molecular genetics approach to determine why this cause of kidney failure runs in families (familial FSGS). Through these efforts our group have identified mutations in TRPC6 (Winn et al. PMID: 15879175), ANLN (Gbadegesin et al. PMID: 24676636) as causes of familial FSGS. In addition, we have shown that mutations in WT1 may also cause adult onset familial FSGS (Hall et al, PMID: 25145932). In collaboration with other investigators, we also showed that mutations in PLCE1 (Hinkes et al. PMID: 17086182), COQ6 (Heeringa et al. PMID: 21540551), ARHGAP24 (Akilesh et al. PMID: 21911940) are causes of familial FSGS. More recently, our group showed that rare pathogenic variants in the gene RCAN1 could cause familial FSGS and other chronic kidney diseases (Lane et al. JASN 2021: In press). In addition, we have continued to characterize the mechanisms by which defects in these genes and more than 60 other FSGS/nephrotic syndrome genes can cause disease. We recently identified pathways that may lead us to new treatment for FSGS. We hope that finding the genetic causes of FSGS will eventually lead to prevention and better treatment of the condition.
FSGS RESEARCH REVIEW
Genetics of Kidney Disease Research Update, 2017
Genetics of Kidney Disease Research Update, 2013
News About FSGS Research, Summer 2005
A research team at the Duke Molecular Physiology Institute (DMPI), formerly the Duke Center for Human Genetics, has discovered a gene responsible for one form of chronic kidney disease. The disease, called familial focal segmental glomerulosclerosis, can lead to complete kidney failure and affects 20 percent of patients on dialysis.
The research team at the DMPI has made progress in the search for genes that causes familial FSGS by using linkage analysis on families that have two or more individuals affected by FSGS. This is done by testing many different markers on each chromosome. These markers have different forms called alleles. An individual has two alleles for each chromosomes, having inherited one allele from each parent. Linkage analysis is used to find those markers in which the same alleles are shared by all the FSGS affected individuals in a family. Since the chromosomal location of the shared marker is known, we are able to determine the chromosomal location of the disorder that is being studied, in this case, FSGS. Our linkage analysis has indicated that one form of FSGS is located on chromosome 11. Further research will help to identify the exact location of the gene. Families with affected and unaffected members are necessary to successfully accomplish this work. We are also recruiting individuals with FSGS who do not have a family history of the disease.
A project of this magnitude requires the efforts of many individuals. Experienced DMPI researchers, with the help of interested families, continue the search for the genes that cause familial FSGS.
FSGS Study Team
|Rasheed Gbadegesin, MD||Principal Investigator|
|Gentzon Hall, MD, PhD||Assistant Professor|
|Megan Chryst-Stangl||Lab Research Analyst|
|Brandon Lane, PhD||Postdoctoral Fellow|
|Guanghong Wu||Lab Research Analyst|
Although Dr. Peter J. Conlon has returned to Ireland, he continues his FSGS research collaboration with the DMPI.
DMPI FSGS PUBLICATIONS
As DMPI researchers continue to define the genetic causes of FSGS, they publish their findings in leading academic journals and share their knowledge with colleagues at meetings and conferences.
List of FSGS Research Publications.
FSGS STUDY PARTICIPATION
The DMPI is actively recruiting individuals with AND without a family history of FSGS. Participating families will be asked to contribute the following items of information to the study:
- A family history interview conducted over the telephone
- A detailed medical history
- A blood sample from all participating family members
- A urine sample from all participating family members
Once blood samples are received in the laboratory, the genetic material (DNA) is removed from the white blood cells. The DNA is used to compare the DNA from individuals affected by FSGS with individuals who are not affected by FSGS. The urine sample will be tested for protein. Finding protein in the urine (proteinuria) helps to identify individuals who may be in the early stages of FSGS but who have not yet had any kidney problems.
No individual or family-specific genetic results will be given to study participants. We will share our overall findings with families through periodic newsletters and scientific publications. If a research breakthrough or a genetic test becomes available, we will notify participants.
This research will not give a result in the short term, but we hope that in the next few years the research will allow us to better understand the cause of renal failure, allow us to diagnose it earlier, and develop new treatments to prevent it.
Duke Molecular Physiology Institute Contact:
FSGS Study Coordinator
This study is funded by grants from the National Kidney Foundation and the NIH National Institute of Diabetes and Digestive and Kidney Disease.
ADDITIONAL FSGS INFORMATION
National Kidney Foundation
30 East 33rd Street
New York, NY 10016
Phone:(toll free) (800) 622-9010
Fax: (212) 689-9261
American Kidney Fund
6110 Executive Boulevard, Suite 1010
Rockville, MD 20852
Phone: (toll free) (800) 638-8299
American Association of Kidney Patients
111 South Ashley Drive, #280
Tampa, FL 33602
Phone: (813) 223-7099
Phone: (toll free) (800) 749-2257
Fax: (813) 223-0001
Positive Renal Outreach Program (PROP)
PO Box 32
Maryknoll, NY 10545-0032
National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)
National Kidney and Urologic Diseases Information Clearinghouse (NDUDIC)
3 Information Way
Bethesda, MD 20892-3580
Fax: (301) 907-8906
The NephCure Foundation
15 Waterloo Avenue, Suite 200
Berwyn, PA 19312
Phone: (610) 540 - 0186
Fax: (610) 540 - 0190
Web Site: www.nephcure.org
Other FSGS Links