Abstract: TH-PO485
Frequency of Diagnostic Variants of Kidney Disease in Diabetic Kidney Disease Patients: A Single-Center Investigation
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
- Hashiba, Toyohiro, Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
- Sugawara, Yuka, Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
- Hirakawa, Yosuke, Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
- Sato, Dai, Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
- Inagi, Reiko, Division of Chronic Kidney Disease Pathophysiology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
- Nangaku, Masaomi, Division of Nephrology and Endocrinology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan
Background
Involvement of rare variants in the pathogenesis of lifestyle diseases has not been investigated in detail. The past research showed that diagnostic variants were detected only in 1.6% of cases with diabetic kidney diseases (DKD) (NEJM, 2019), but there was no mention of which cases should be genetically tested. Therefore, we performed a whole genome sequence (WGS) based analysis of pathogenic single nucleotide variants (SNVs) of DKD patients to extract the characteristics of cases with pathogenic SNVs.
Methods
We performed WGS for Japanese patients with clinically diagnosed-DKD. Variants were processed with GATK Best Practices. We defined target variants as those included in the 625 genes associated with Mendelian nephropathy and genitourinary diseases (same as analyzed genes in NEJM 2019) and classified as pathogenic or likely pathogenic by ACMG criteria. Target variants were classified into four categories: glomerulopathy, tubulointerstitial, cystic/ciliopathy, and others.
Results
Of the 79 participants, 66 (84%) were males, 70.3±0.8 ages, and 9 (11%) had a family history of kidney diseases. A total of 25 patients (32%) had the target variants, all heterozygously. There were no significant differences in clinical information such as level of albuminuria between cases with and without the target variants. There were 10 cases with the variants in genes WT1, ASXL1, PAX2, ALPL, ABCC6, and GCM2, which reportedly show an autosomal dominant (AD) manner of inheritance. Only 2 of these 10 cases had a family history of kidney disease.
Conclusion
Among clinically diagnosed Japanese DKD patients, a considerable number had kidney-related pathologic variants, which were unexpectedly large compared to the previous report. It was difficult to determine from clinical presentation or family history which cases had the target variants.
Gene names of the detected target variants are shown along with their category classification and the number of persons with them. Stripes indicate AD pattern of inheritance.