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

J Am Soc Nephrol. 2018 Jun;29(6):1772-1779. doi: 10.1681/ASN.2017111200. Epub 2018 Apr 13.


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.

Keywords: cystic kidney; end-stage renal disease; genetic renal disease; human genetics; transplantation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adolescent
  • Adult
  • Age Factors
  • Cytoskeletal Proteins
  • Female
  • Gene Deletion
  • Gene Dosage
  • Homozygote
  • Humans
  • Incidence
  • Kidney Diseases, Cystic / complications
  • Kidney Diseases, Cystic / epidemiology*
  • Kidney Diseases, Cystic / genetics*
  • Kidney Failure, Chronic / genetics*
  • Kidney Failure, Chronic / therapy
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prevalence
  • Young Adult


  • Adaptor Proteins, Signal Transducing
  • Cytoskeletal Proteins
  • Membrane Proteins
  • NPHP1 protein, human