Abstract: TH-PO456
Genetic Causes of Focal Segmental Glomerulosclerosis in Koreans
Session Information
- Genetic Diseases: Glomerulopathies - I
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Shin, Hyeri, Seoul National University Children's Hospital, Seoul, Korea (the Republic of)
- Choi, Naye, Seoul National University Children's Hospital, Seoul, Korea (the Republic of)
- Lee, Hyeonju, Seoul National University Children's Hospital, Seoul, Korea (the Republic of)
- Kim, Ji hyun, Seoul National University Bundang Hospital, Seongnam, Korea (the Republic of)
- Lee, Hajeong, Seoul National University Hospital Department of Internal Medicine, Jongno-gu, Seoul, Korea (the Republic of)
- Ahn, Yo Han, Seoul National University Children's Hospital, Seoul, Korea (the Republic of)
- Suh, Jin-Soon, Catholic University of Korea Bucheon Saint Mary's Hospital, Bucheon, Gyeonggi-do, Korea (the Republic of)
- Kang, Hee Gyung, Seoul National University Children's Hospital, Seoul, Korea (the Republic of)
Background
Focal segmental glomerulosclerosis (FSGS) is a relatively common pathologic findings of nephrotic syndrome or chronic kidney disease (CKD) presenting proteinuria. Genetic FSGS, usually not responding to immunosuppressive medications, is more common in younger patients and those who have a family history of kidney disease. Common genetic causes of FSGS include mutations reported COL4A mutations in families, but those of Korean population have not been well investigated.
Methods
The Korean Genetic Kidney Disease Cohort study is enrolling patients with kidney diseases of presumably genetic origin since 2021. Clinical characteristics of the cases were collected by the referring physicians and the genomic DNA of the enrolled cases were sequenced by multiple parallel sequencing of whole exome sequencing. Pathogenicity of variants were interpretated according to the American College of Medical Genetics (ACMG) guideline referring the resources of gnomAD (genome Aggregation Database), ClinVar (National Center for Biotechnology Information ClinVar Database), VarSome and other in silico prediction tools.
Results
Of a total 453 prospective cases of the our cohort, 124 cases (27.4%, Male:Female 64:60, mean age of diagnosis 20.8 year (range 0-78.7 years)) had pathological diagnosis of FSGS. Among them, 20.9% had a positive family history. Genetic diagnosis was obtained in 40.3% (n=50), among which COL4A3-5 (n=8) were the most commonly found causative gene, followed by NPHS1 (n=6), PAX2 (n=5), WT1 (n=4), COQ6/8B (n=4), NUP107 (n=3), TRPC6 (n=3), LAMA5 (n=2), MYH9 (n=2), MAFB (n=1). Gene testing changed the diagnosis in 8 (FSGS to Alport syndrome (AS)), lead to extrarenal manifestation screening in 8 (AS, PAX2, MYH9, and MAFB), and provided information on potential treatment (coenzyme Q10) in 4 with COQ6/8b mutations.
Conclusion
We found that proportions of causative genes in Korean FSGS are different from previous results of Western countries. Similar to the literature, gene testing was useful in obtaining more precise diagnosis and guiding management.