Abstract: FR-PO661
Familial Variability of Disease Progression in Autosomal Dominant Alport Syndrome: Results from SHRAS
Session Information
- Genetic Kidney Diseases: Cohort Studies - Genetic Associations and Diagnoses
October 25, 2024 | Location: Exhibit Hall, 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
- Dai, Xuantong, Renal Division, Department of Internal Medicine, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Hu, Ningning, Renal Division, Department of Internal Medicine, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Jiang, Gengru, Renal Division, Department of Internal Medicine, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Lin, Fujun Fiona, Renal Division, Department of Internal Medicine, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Background
Autosomal dominant Alport syndrome (ADAS), caused by heterozygous COL4A3 or COL4A4 pathogenic variants, is characterized by a large variability of disease progression. This study aims to evaluate the intrafamilial variability of disease progression and the relevant predictors in Chinese ADAS patients from the Shanghai Registry of Alport syndrome (SHRAS).
Methods
SHRAS, part of the Shanghai Registry of Genetic Kidney Disease, performed collection of clinical, and genetic data of ADAS patients referred from 14 leading tertiary hospitals across China since 2006. In kindreds with ≥ 2 affected individuals, discordant disease progression were evaluated in 2 categories: age at onset of proteinuria and stage 3 chronic kidney disease (CKD). Marked intrafamilial variability was defined as the onset age across 2 categories differed ≥ 20 years in at least 2 patients in one kindred, or in kindred with both pediatric and adult patients, proteinuria or stage 3 CKD developed in at least 1 pediatric patient while the phenotype of adult patient was isolated hematuria.
Results
Among 73 kindreds of 311 ADAS patients (118 pediatric and 193 adult patients), 31 kindreds (42.47%) of 72 patients (21 pediatric and 51 adult patients) were deemed as discordant disease progression. Intrafamilial variability was not associated with family size nor genotype (Table 1). Multivariate mixed-effects model revealed concomitant kidney disease and disease onset age as risk factors of variability (Figure 1).
Conclusion
In ADAS cohort of SHRAS, marked intrafamilial variability of disease progression was observed. Our findings didn’t reveal a significant genotype influence on intrafamilial variability, which necessitates a more thorough identification of relevant clinical and genotypic factors.