Whole-exome sequencing reveals GRHPR gene mutation in a 4-year-old girl with chronic kidney disease - a case report

Sep 29, 2026

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Whole-exome sequencing is used to identify a genetic cause of chronic kidney disease in a pediatric case with a family history. A 4-year-old girl evaluated for black urine was suspected to have renal pathology and underwent genetic testing by WES. A missense variant in the GRHPR gene (c.494 G>A) was found in the patient and also in her 27-year-old father. Kidney stones were removed by extracorporeal shock wave lithotripsy, with post-procedure stability and discharge, supporting precision diagnosis and family risk assessment.

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Introduction

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Case Report Whole-exome sequencing reveals GRHPR gene mutation in a 4-year-old girl with chronic kidney disease: a case report Bakhtawar Farooq, MBBS, PhDa,b , Zahid H. Qureshi, MBBS, PhDc , Madeeha S. Lodhi, PhDa , Muhammad Faisal, PhDd , Esha Khan, MBBSe , Muddassir Khalid, MBBSe ,* Introduction and importance: Chronic kidney disease (CKD) is recognized as one of the leading causes of human death. This case highlights the importance of whole-exome sequencing (WES) and genetic diagnosis in families. Case Presentation: A 4-year-old girl (subject) was diagnosed with CKD along with her father, grandfather, and grandmother. The subject was first evaluated at 4 years of age because of black urine problem. On early diagnosis, it was kidney stones. She was suspected to be affected with kidney disorder by ultrasound and is being evaluated for the presence genetic variations by WES. We identified a missense variation in GRHPR gene c.494 G>A in subject, and her 27-year-old father was also identified with the same variation in the GRHPR gene. On follow-up, kidney stones were removed via extracorporeal shock wave lithotripsy (ESWL) . Following ESWL sections, the subject was stable and sent home. Clinical discussion: Genetic diagnoses are essential for identifying diseases, which aid in early diagnosis and control to spread within families. This case highlights the value of advanced genetic testing in nephrology for precision diagnosis and family risk assessment. Conclusion: A multidisciplinary approach and timely intervention in CKD are vital to prevent complications in families. Keywords: case report, chronic kidney disease, CKD, genetics, WES, whole-exome sequencing Introduction Chronic kidney disease (CKD) is a global health concern marked by progressive renal function decline, primarily caused by diabetes, hypertension, heart issues, obesity, family history, and smoking[1] . CKD is characterized by a decrease in estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1 .73 m2 and kidney damage markers presented for more than 3 months[2] . The prevalence of CKD in families is rising, but awareness of CKD is low[3] . The progression of CKD is significantly impacted by an underlying genetic disorder[3] . The diagnosis of monogenic kidney disorders is essential, as it can profoundly influence a patient’s prognosis and clinical management, including the potential for aInstitute ofMolecular Biology and Biotechnology, The University of Lahore, Lahore, Pakistan, bDepartment of Biochemistry, Nishtar Medical University, Multan, Pakistan, cDepartment of Physiology, Multan Medical and Dental College, Multan, Pakistan, dDepartment of Biotechnology, MNS-University of Agriculture, Multan, Pakistan and eDepartment of Medicine, Nishtar Medical University, Multan, Pakistan Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. *Corresponding author. Address: Department of Medicine, Nishtar Medical University, Multan 60000, Pakistan. Tel.: +[923330333544. E-mail: dr.muddassirkhalid@gmail.com](923330333544. E-mail: dr.muddassirkhalid@gmail.com)[ ](923330333544. E-mail: dr.muddassirkhalid@gmail.com)(M. Khalid). Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Annals of Medicine & Surgery (2026) 88:929–934 Received 23 September 2025; Accepted 4 December 2025 Published online 18 December 2025 [http://dx.doi.org/10.1097/MS9.0000000000004596](http://dx.doi.org/10.1097/MS9.0000000000004596) targeted treatments[4] . Primary Hyperoxaluria Type 2 (PH2), caused by mutations in the GRHPR gene, disrupts the normal metabolism of glyoxylate – metabolism characterized by overproduction of oxalate – leading to oxalate nephr

FAQs

What genetic finding was identified in the 4-year-old girl with chronic kidney disease?

A missense variant in the GRHPR gene, c.494 G>A, was identified by whole-exome sequencing.

How was the family history incorporated into the diagnosis?

The same GRHPR gene variant was detected in the patient’s 27-year-old father, supporting a heritable genetic basis.

What treatment was performed for kidney stones in this case?

Kidney stones were removed via extracorporeal shock wave lithotripsy (ESWL), after which the patient was stable and discharged.

Sep 29, 2026

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