| Autor: |
Orisio, Silvia, Noris, Marina, Rigoldi, Miriam, Bresin, Elena, Perico, Norberto, Trillini, Matias, Donadelli, Roberta, Perna, Annalisa, Benigni, Ariela, Remuzzi, Giuseppe |
| Zdroj: |
Nephron; May 2024, Vol. 148 Issue: 5 p273-291, 19p |
| Abstrakt: |
Background:Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited disease of the kidney. It occurs in adulthood but is also rarely diagnosed in early childhood. The majority of the disease-causing variants observed in ADPKD patients are in two genes: PKD1and PKD2. Methods:237 patients from 198 families with a clinical diagnosis of ADPKD were screened for PKD1and PKD2genetic variants using Sanger sequencing and multiple ligation-dependent probe amplification analysis. Results:Disease-causing (diagnostic) variants were identified in 173 families (211 patients), 156 on PKD1and 17 on PKD2. Variants of unknown significance were detected in 6 additional families, while no mutations were found in the remaining 19 families. Among the diagnostic variants detected, 51 were novel. In ten families, seven large rearrangements were found and the molecular breakpoints of 3 rearrangements were identified. Renal survival was significantly worse for PKD1-mutated patients, particularly those carrying truncating mutations. In patients with PKD1truncating (PKD1-T) mutations, disease onset was significantly earlier than in patients with PKD1non-truncating variants or PKD2-mutated patients. Conclusions:Comprehensive genetic testing confirms its utility in diagnosing patients with ADPKD and contributes to explaining the clinical heterogeneity observed in this disease. Moreover, the genotype-phenotype correlation can allow for a more accurate disease prognosis. |
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