Biallelic NPHP3 Variants Causing Late Onset Chronic Kidney Insufficiency in Nephronophthisis: A Case Report

ABSTRACT Emerging evidence suggests that the overall prevalence of nephronophthisis (NPHP) in adult‐onset end‐stage kidney disease (ESKD) is very likely underestimated. Thus, a comprehensive understanding of the genetic basis and clinicopathologic features of adult‐onset NPHP is essential. In this case, we report a 38‐year‐old woman who exhibited no growth disorders or urinary abnormalities in prior physical examinations. However, at 38 years of age, she presented with renal dysfunction (eGFR 29.5 mL/min/1.73 m 2 ). Urine tests revealed a low specific gravity of urine, but no proteinuria or microscopic hematuria, while urinary (α1‐MG) was elevated (137 mg/L). Extrarenal phenotypes were absent. For a definitive diagnosis, a renal biopsy was conducted. Light microscopic findings showed established irregular microcystic dilatation in the tubules, irregular focal lamellation of the tubular basement membrane and moderate fibrosis in the interstitial area. Genetic analysis identified biallelic NPHP3 variants in trans: c.1047C>A (p.Tyr349Ter) non‐sense variant and c.3725A>G (p.Tyr1242Cys) missense variant., leading to a definitive diagnosis of NPHP. This case highlights NPHP3 as an appreciable genetic cause for adult‐onset nonsyndromic NPHP. Further studies are required to clarify the genotype–phenotype correlations of NPHP in adults.