Abstract
RATIONALE & OBJECTIVE
Monoallelic predicted Loss-of-Function (pLoF) variants in IFT140 have recently been associated with an autosomal dominant polycystic kidney disease (ADPKD)-like phenotype. This study sought to enhance the characterization of this phenotype.
STUDY DESIGN
Case series.
SETTING & PARTICIPANTS
Seventy-five among 2797 European individuals with ADPKD-like phenotypes who underwent genetic testing that revealed pLoF IFT140-variants.
FINDINGS
The 75 individuals (median age 56 years, 53.3% females) were from 61 families and were found to have 41 different monoallelic pLoF IFT140-variants. The majority of individuals presented with large, exophytic kidney cysts (median [range] total kidney volume 688 ml [201-4139]), and 90.2% were classified using the Mayo Imaging Classification as Mayo Class 2A. Arterial hypertension was present in 50.7% of the individuals (median [range] age at diagnosis 59 years [29-73]). Only one patient developed kidney failure (at age 69 years). A significant difference in age-adjusted eGFR between male and female patients was observed (P<0.001). 56.3% of the individuals over the age of 60 years had an eGFR less than 60ml/min/1.73m$^{2}$. The estimated genetic prevalence of monoallelic pLoF IFT140 variants was 19.76 (95%CI=18.8-20.7) and 27.89 (95%CI=23.8-31.9) per 10,000 in the Genome Aggregation Database and the 100,000 Genomes Project (100kG), respectively. CyKD (ICD-10 Q61) was associated with pLoF IFT140 variants (P=2.9x10$^{-9}$, OR=5.6 (3.3-9.2)) only in 100kG.
STUDY LIMITATIONS
Retrospective study; younger patients and patients with milder forms of IFT140-related CyKD may not be diagnosed.
CONCLUSIONS
Individuals with monoallelic IFT140 pLoF variants are likely to develop kidney cysts atypical of classical ADPKD and generally have a favorable kidney prognosis.
Zagorec, Nikola