This study evaluates the characterization of this atypical phenotype and focuses on 75 patients with ADPKD-like phenotypes with 41 different monoallelic predicted loss-of-function IFT140 variants.
Autosomal dominant polycystic kidney disease (ADPKD) is caused by gene mutations in the PKD1 or PKD2 genes. Common symptoms include pain in the back and sides, between the ribs and hips, headaches, hematuria, and high blood pressure. The condition often eventually leads to kidney failure. Recently, associations have been found between monoallelic predicted loss-of-function variants in IFT140 and ADPKD-like phenotypes.
The majority of participants presented with large, exophytic kidney cysts. Arterial hypertension was present in 50.7% of patients. A significant difference was observed in the estimated glomerular filtration rate between male and female patients, and 56.3% of patients over the age of 60 years had an estimated glomerular filtration rate of <60mL/min/1.73m2. Only one patient developed kidney failure.
The estimated genetic prevalence of monoallelic predicted loss-of-function IFT140 variants was 19.76 per 10,000 in the Genome Aggregation Database and 27.89 per 10,000 in the 100,000 Genomes Project. Only cystic kidney disease was associated with predicted loss-of-function IFT140 variants in the 100,000 Genomes Project.
Overall, it was observed that patients with monoallelic IFT140 predicted loss-of-function variants are likely to develop atypical kidney cysts compared to those in classic ADPKD. Kidney prognosis is also generally favorable.
To learn more about rare kidney conditions, visit https://checkrare.com/diseases/kidney-and-urinary-diseases/
References:
Zagorec N, et al. Clinical Spectrum and Prognosis of Atypical Autosomal Dominant Polycystic Kidney Disease Caused by Monoallelic Pathogenic Variants of IFT140. American Journal of Kidney Diseases. 2025 [in press]. https://www.ajkd.org/article/S0272-6386(24)01126-0/abstract
Autosomal Dominant Polycystic Kidney Disease. National Institute of Diabetes and Digestive and Kidney Diseases. 2024. https://www.niddk.nih.gov/health-information/kidney-disease/polycystic-kidney-disease/autosomal-dominant-pkd