Whole Exome Sequencing Reveals a XPNPEP3 Novel Mutation Causing Nephronophthisis in a Pediatric Patient

Alizadeh, Rasoul; Jamshidi, Sanaz; Keramatipour, Mohammad; Moeinian, Parisa; Hosseini, Rozita; Otukesh, Hasan; Talebi, Saeed

doi:10.29252/ibj.24.6.400

Whole Exome Sequencing Reveals a XPNPEP3 Novel Mutation Causing Nephronophthisis in a Pediatric Patient

Authors

Rasoul Alizadeh ¹

Sanaz Jamshidi ¹

Mohammad Keramatipour ²

Parisa Moeinian ¹

Rozita Hosseini ³

Hasan Otukesh ⁴

Saeed Talebi ¹

¹ Department of Medical Genetics and Molecular Biology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

² Department of Medical Genetics, Schools of Medicine, Tehran University of Medical Sciences, Tehran, Iran

³ Department of Pediatrics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

⁴ Ali Asghar Children's Hospital, Tehran, Iran

10.29252/ibj.24.6.400

Abstract

Background: 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. Methods: 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’ confirmation and segregation analysis. Results: Clinical and paraclinical investigations of the patient was not informative. Using WES, we could detect a novel homozygous frameshift mutation in XPNPEP3 (NM_022098.2: c.719_720insA; p. Q241Tfs*13), and by Sanger sequencing, we demonstrated an insertion in XPNPEP3. Conclusion: The homozygous genotype of the novel p.Q241Tfs*31 variant in XPNPEP3 may cause NPHP in the early childhood age.

Keywords

Nephronophthisis

Whole Exome Sequencing

XPNPEP3