NPHP1 (Nephrocystin-1) Gene Deletions Cause Adult-Onset ESRD

Rozemarijn Snoek, Jessica van Setten, Brendan J Keating, Ajay K Israni, Pamala A Jacobson, William S Oetting, Arthur J Matas, Roslyn B Mannon, Zhongyang Zhang, Weijia Zhang, Ke Hao, Barbara Murphy, Roman Reindl-Schwaighofer, Andreas Heinzl, Rainer Oberbauer, Ondrej Viklicky, Peter J Conlon, Caragh P Stapleton, Stephan J L Bakker, Harold SniederEdith D J Peters, Bert van der Zwaag, Nine V A M Knoers, Martin H de Borst, Albertien M van Eerde

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Background Nephronophthisis (NPH) is the most prevalent genetic cause for ESRD in children. However, little is known about the prevalence of NPH in adult-onset ESRD. Homozygous full gene deletions of the NPHP1 gene encoding nephrocystin-1 are a prominent cause of NPH. We determined the prevalence of NPH in adults by assessing homozygous NPHP1 full gene deletions in adult-onset ESRD.

Methods Adult renal transplant recipients from five cohorts of the International Genetics and Translational Research in Transplantation Network (iGeneTRAiN) underwent single-nucleotide polymorphism genotyping. After quality control, we determined autosomal copy number variants (such as deletions) on the basis of median log2 ratios and B-allele frequency patterns. The findings were independently validated in one cohort. Patients were included in the analysis if they had adult-onset ESRD, defined as start of RRT at >= 18 years old.

Results We included 5606 patients with adult-onset ESRD; 26 (0.5%) showed homozygous NPHP1 deletions. No donor controls showed homozygosity for this deletion. Median age at ESRD onset was 30 (range, 18-61) years old for patients with NPH, with 54% of patients age >= 30 years old. Notably, only three (12%) patients were phenotypically classified as having NPH, whereas most patients were defined as having CKD with unknown etiology (n=11; 42%).

Conclusions Considering that other mutation types in NPHP1 or mutations in other NPH-causing genes were not analyzed, NPH is a relatively frequent monogenic cause of adult-onset ESRD. Because 88% of patients had not been clinically diagnosed with NPH, wider application of genetic testing in adult-onset ESRD may be warranted.

Original languageEnglish
Pages (from-to)1772-1779
Number of pages8
JournalJournal of the American Society of Nephrology
Issue number6
Early online date13-Apr-2018
Publication statusPublished - Jun-2018


  • genetic renal disease
  • transplantation
  • end-stage renal disease
  • human genetics
  • cystic kidney

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