en Molecular Genetics & Genomics Molecular Genetics & Genomics مقاله موردی Case Report <strong>Background: </strong>Nephronophthisis (NPHP) is a progressive tubulointestinal kidney condition that demonstrates an AR inheritance pattern. Up to now, more than 20 various genes have been detected for NPHP, with NPHP1 as the first one detected. X-prolyl aminopeptidase 3 (XPNPEP3) mutation is related to NPHP-like 1 nephropathy and late onset NPHP. <strong>Methods:</strong> The proband (index patient) had polyuria, polydipsia and chronic kidney disease and was clinically suspected of NPHP. After the collection of blood sample from proband and her parents, whole exome sequencing (WES) was performed to identify the possible variants in the proband from a consanguineous marriage. The functional importance of variants was estimated by bioinformatic analysis. In the affected proband and her parents, Sanger sequencing was conducted for variants&rsquo; confirmation and segregation analysis. <strong>Results</strong>: Clinical and paraclinical investigations of the patient was not informative. Using WES, we could detect a novel homozygous frameshift mutation in <em>XPNPEP3</em> (NM_022098.2: c.719_720insA; p. Q241Tfs*13), and by Sanger sequencing, we demonstrated an insertion in <em>XPNPEP3</em>. <strong>Conclusion</strong>: The homozygous genotype of the novel p.Q241Tfs*31 variant in <em>XPNPEP3 </em>may cause NPHP in the early childhood age. Nephronophthisis, Whole exome sequencing, XPNPEP3 405 408 http://ibj.pasteur.ac.ir/browse.php?a_code=A-10-1-828&slc_lang=en&sid=1 Rasoul Alizadeh 0000-0002-6813-6727 No Department of Medical Genetics and Molecular Biology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Sanaz Jamshidi 0000-0002-3937-6043 No Department of Medical Genetics and Molecular Biology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Mohammad Keramatipour 0000-0002-5803-4209 No Department of Medical Genetics, Schools of Medicine, Tehran University of Medical Sciences, Tehran, Iran Parisa Moeinian 0000-0003-1219-495X No Department of Medical Genetics and Molecular Biology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Rozita Hosseini 0000-0003-2851-4727 No Department of Pediatrics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran Hasan Otukesh 0000-0003-2071-517X No Ali Asghar Children's Hospital, Tehran, Iran Saeed Talebi 0000-0002-8055-9335 Yes Department of Medical Genetics and Molecular Biology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran