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Nephronophthisis 13: implications of its association with Caroli disease and altered intracellular localization of WDR19 in the kidney

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Abstract

Background

Nephronophthisis 13 (NPHP 13) is associated with mutations in the WDR19 gene, which encodes for a protein in the intraflagellar transport complex. Herein, we describe six additional cases accompanied by Caroli syndrome or disease.

Methods

Targeted exome sequencing covering 96 ciliopathy-related genes was performed for 48 unrelated Korean patients with a clinical suspicion of NPHP. Mutations were confirmed by Sanger sequencing. We evaluated the expression of WDR19 in the biopsied kidney by immunohistochemistry in patients and controls.

Results

We detected three (3/48, 6.3 %) unrelated index cases with WDR19 mutations. One of the cases involved two siblings with the same mutation. Later, we detected an additional index case with a similar phenotype of kidney and liver involvement by Sanger sequencing of WDR19. The p.R1178Q mutation was common in all patients. All of the six affected patients from four families progressed to chronic kidney disease. Of note, all six patients had Caroli syndrome or disease. Immunohistochemistry for WDR19 showed localized expression along the luminal borders of the renal tubular epithelium in controls, whereas it showed diffuse cytoplasmic staining in the affected patients.

Conclusions

Caroli disease is a major extra-renal phenotype associated with mutations in WDR19 in the Korean population. In this study, we visually validated the expression pattern of mutant WDR19 protein in the kidneys of NPHP 13 patients. More data are needed to identify the true frequency of p.R1178Q. Functional studies including transfection assay will provide solid grounds for the pathogenicity of each mutation.

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Acknowledgments

We thank Young-Hun Choi and Hyungjin Kim (Department of Radiology, Seoul National University Children’s Hospital) for reviewing the radiological images. We also thank Younghoon Kim for helping with the preparation of the control samples for immunohistochemistry. This study was supported by a grant (HI12C0014) from the Korea Healthcare technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea.

Disclosures

None.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Seoul National University Children’s Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul, 110-744, Korea

    Jiwon M. Lee, Yo Han Ahn, Hee Gyung Kang, II Soo Ha & Hae II Cheong

  2. Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, Korea

    Hee Gyung Kang & Hae II Cheong

  3. Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea

    II Soo Ha & Hae II Cheong

  4. Department of Pathology, Seoul National University Hospital, Seoul, Korea

    Kyoungbun Lee & Kyung Chul Moon

  5. Department of Pediatrics, Asan Medical Center, Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea

    Joo Hoon Lee & Young Seo Park

  6. Department of Pathology, Asan Medical Center, Children’s Hospital, University of Ulsan College of Medicine, Seoul, Korea

    Yong Mee Cho

  7. Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology (SAIHST), Sungkyunkwan University, Seoul, Korea

    Jun-Seok Bae

  8. Samsung Genome Institute, Samsung Medical Center, Seoul, Korea

    Jun-Seok Bae, Nayoung K. D. Kim & Woong-Yang Park

  9. Sungkyunkwan University School of Medicine, Seoul, Korea

    Woong-Yang Park

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  1. Jiwon M. Lee
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  2. Yo Han Ahn
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Correspondence to Hae II Cheong.

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Lee, J.M., Ahn, Y.H., Kang, H.G. et al. Nephronophthisis 13: implications of its association with Caroli disease and altered intracellular localization of WDR19 in the kidney. Pediatr Nephrol 30, 1451–1458 (2015). https://doi.org/10.1007/s00467-015-3068-8

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  • DOI: https://doi.org/10.1007/s00467-015-3068-8

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