| Title: |
NPHP1 (Nephrocystin-1) gene deletions cause adult-onset ESRD |
| Authors: |
Snoek, Rozemarijn; Van Setten, Jessica; Keating,Brendan J.; Israni,Ajay K.; Jacobson,Pamala A.; Oetting,William S.; Matas,Arthur J.; Mannon,Roslyn B.; Zhang,Zhongyang; Zhang,Weijia; Hao,Ke; Murphy,Barbara; Reindl-Schwaighofer,Roman; Heinzl,Andreas; Oberbauer,Rainer; Viklicky,Ondrej; Conlon,Peter J.; Stapleton,Caragh P.; Bakker, Stephan J.L.; Snieder,Harold; Peters,Edith D.J.; Van Der Zwaag, Bert; Knoers, Nine V.A.M.; De Borst,Martin H.; Van Eerde, Albertien M.; Genetica; CMM; Genetica Groep Van Haaften; Device; Onderzoek Precision medicine; Affectieve & Psychotische Med.; Genetica Sectie Genoomdiagnostiek; Child Health; Genetica Klinische Genetica |
| Publication Year: |
2018 |
| Subject Terms: |
Taverne; Nephrology |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text/plain |
| Language: |
English |
| ISSN: |
1046-6673 |
| Relation: |
https://dspace.library.uu.nl/handle/1874/376986 |
| Availability: |
https://dspace.library.uu.nl/handle/1874/376986 |
| Rights: |
info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.9D6CCBA4 |
| Database: |
BASE |