Abstract: SA-PO0120
Novel NEK8 Variant Associated with Adult-Onset ADPKD
Session Information
- ADPKD and Cystic Kidney Disease - 3
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1201 Genetic Diseases of the Kidneys: Cystic (Monogenic)
Authors
- Yacoub, Fadi, Mercy Cedar Rapids, Cedar Rapids, Iowa, United States
- Severe, Bailey, Natera Inc, Austin, Texas, United States
- Westemeyer, Margaret, Natera Inc, Austin, Texas, United States
- Punj, Sumit, Natera Inc, Austin, Texas, United States
Introduction
Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited kidney diseases, with PKD1 and PKD2 accounting for approximately 93% of genetically resolved cases. Recently several minor genes have been implicated in causing ADPKD or ADPKD-like phenotypes. NEK8 is now considered a minor ADPKD gene with well-supported evidence of pathogenicity. To date, 21 affected individuals have been reported to have heterozygous variants in NEK8. The implicated missense variants were primarily located in the kinase domain and all patients presented with uniformly severe, neonatal-onset cystic kidney disease. Here we present the first report of adult-onset ADPKD-NEK8, demonstrating preserved renal function into the eighth decade.
Case Description
An 80-year-old female presented with CKD Stage 3b due to polycystic kidney disease. Her eGFR was 31 mL/min/1.73m2 and ultrasound and MRI demonstrated bilaterally enlarged kidneys with multiple cysts. In 2016, the patient was diagnosed with stress-induced cardiomyopathy, which later resolved to a normal ejection fraction. Notable family history was consistent with an autosomal dominant PKD inheritance pattern with a maternal grandfather who died at age 54, and her mother, aunt, and brother all requiring dialysis in their 60s.
Genetic testing via a broad kidney gene panel (the RenasightTM test) identified a novel heterozygous missense variant c.675C>A (p.Asp225Glu) in NEK8.
Discussion
This case represents the first report of the NEK8 variant c.675C>A (p.Asp225Glu) and the mildest NEK8-associated ADPKD phenotype to date. The attenuated phenotype and late disease onset observed in this case demonstrates that there is a spectrum of disease severities associated with ADPKD-NEK8, significantly expanding the phenotypic spectrum described thus far. Further understanding the range and severity of clinical manifestations, and the genotype-phenotype relationships associated with ADPKD-NEK8 will help inform prognosis and management of these patients.