Abstract: PO1337
Whole-Exome Sequencing Reveals a Monogenic Cause of Disease in 26% of 335 Families with Steroid-Resistant Nephrotic Syndrome
Session Information
- Genetic Diseases of the Kidneys: Non-Cystic - II
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1002 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Schneider, Ronen, Boston Children's Hospital, Boston, Massachusetts, United States
- Deutsch, Konstantin, Boston Children's Hospital, Boston, Massachusetts, United States
- Onuchic-Whitford, Ana C., Boston Children's Hospital, Boston, Massachusetts, United States
- Yousef, Kirollos, Boston Children's Hospital, Boston, Massachusetts, United States
- Zahoor, Muhammad Y., Boston Children's Hospital, Boston, Massachusetts, United States
- Nicolas Frank, Camille H., Boston Children's Hospital, Boston, Massachusetts, United States
- Buerger, Florian, Boston Children's Hospital, Boston, Massachusetts, United States
- Shril, Shirlee, Boston Children's Hospital, Boston, Massachusetts, United States
- Somers, Michael J., Boston Children's Hospital, Boston, Massachusetts, United States
- Hildebrandt, Friedhelm, Boston Children's Hospital, Boston, Massachusetts, United States
Background
Steroid resistant nephrotic syndrome (SRNS) overwhelmingly progresses to end-stage renal disease. To date, more than 59 monogenic genes have been identified to cause SRNS. We previously detected causative mutations in 25% using whole exome sequencing (Warejko CJASN 13:53, 2018) and in 29.5% of patients with SRNS using targeted panel sequencing (Sadowski JASN 26:1279, 2015). However, whole exome sequencing (WES) has become more accessible, with the advantage of detecting not only known monogenic causes of SRNS, but also novel candidate NS-causing genes.
Methods
We employed whole exome sequencing (WES) to detect monogenic causes of SRNS in a large international cohort of 335 families with SRNS presenting before the age of 25 years.
Results
Samples were recruited from April, 1998 to December, 2018 (21 years). WES was performed at the Yale Center of Mendelian Genomics. First, we examined the WES data for mutations in 59 genes known to cause SRNS. In 87/335 families (26%), we identified mutations in 22 of the known genes. There were also 7 genes that were identified as phenocopies of SRNS e. g. COL4A3. In 58 families (17.3%), we have identified mutations in a potential novel candidate gene for SRNS. We found a 48.1% solve rate in individuals with high homozygosity by decent and 15.4% solve rate in non-homozygous individuals, recapitulating similar solve fractions to what has been previously published (Sadowski 2015; Warejko 2017).
Conclusion
This study confirms that ~26% of families with NS in our cohort are due to monogenic causes. WES is a viable way to diagnose the underlying cause of NS in children and young adults, and to suggest novel monogenic candidate genes of NS.
Funding
- Other NIH Support