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Kidney Week

Abstract: FR-PO963

Genomic Background of Adults with Suspected Ciliopathy on Renal Biopsy

Session Information

Category: Genetic Diseases of the Kidney

  • 1001 Genetic Diseases of the Kidney: Cystic

Authors

  • Fujimaru, Takuya, Tokyo Medical and Dental University, Tokyo, Japan
  • Mori, Takayasu, Tokyo Medical and Dental University, Tokyo, Japan
  • Mandai, Shintaro, Tokyo Medical and Dental University, Tokyo, Japan
  • Chiga, Motoko, Tokyo Medical and Dental University, Tokyo, Japan
  • Kikuchi, Hiroaki, Tokyo Medical and Dental University, Tokyo, Japan
  • Ando, Fumiaki, Tokyo Medical and Dental University, Tokyo, Japan
  • Mori, Yutaro, Tokyo Medical and Dental University, Tokyo, Japan
  • Susa, Koichiro, Tokyo Medical and Dental University, Tokyo, Japan
  • Isobe, Kiyoshi, Tokyo Medical and Dental University, Tokyo, Japan
  • Iimori, Soichiro, Tokyo Medical and Dental University, Tokyo, Japan
  • Nomura, Naohiro, Tokyo Medical and Dental University, Tokyo, Japan
  • Naito, Shotaro, Tokyo Medical and Dental University, Tokyo, Japan
  • Okado, Tomokazu, Tokyo Medical and Dental University, Tokyo, Japan
  • Rai, Tatemitsu, Tokyo Medical and Dental University, Tokyo, Japan
  • Nagatsuji, Katsushi, Osaka City General Hospital, Osaka, Japan
  • Nagahama, Kiyotaka, Kyorin University, Tokyo, Japan
  • Mishima, Eikan, Tohoku University, Miyagi, Japan
  • Mochizuki, Toshio, Tokyo Woman's Medical University, Tokyo, Japan
  • Sekine, Akinari, Toranomon Hospital, Tokyo, Japan
  • Hoshino, Junichi, Toranomon Hospital, Tokyo, Japan
  • Ubara, Yoshifumi, Toranomon Hospital, Tokyo, Japan
  • Uchida, Shinichi, Tokyo Medical and Dental University, Tokyo, Japan
  • Sohara, Eisei, Tokyo Medical and Dental University, Tokyo, Japan
Background

In adult patients, ciliopathy is often difficult to make a precise diagnosis based on clinical features, because they usually have no specific findings such as retinitis pigmentosa or liver dysfunction. Furthermore, it is impossible to make a definitive genetic diagnosis by renal biopsy. Therefore, genetic testing is crucial for precise diagnosis and clinical management of the patients and their families.

Methods

We investigated 17 adult patients who were suspected ciliopathy by renal biopsy. Their pathological findings were tubular dilatation or thickening and lamellation of tubular basement membranes. All patients had no extrarenal findings (retinitis pigmentosa and liver function disorder) and no family history of ciliopathy. Comprehensive genetic testing was performed using capture-based next-generation sequencing for 69 genes that cause nine types of hereditary cystic kidney diseases (autosomal dominant polycystic kidney disease, autosomal recessive polycystic kidney disease, nephronophthisis, Joubert syndrome, Meckel syndrome, Senior-Loken syndrome, Bardet-Biedl syndrome, autosomal dominant tubulointerstitial kidney disease, etc.).

Results

Median age at renal biopsy was 55 (17–84) years old and seven patients (41%) were male. Through our analysis, two patients had homozygous full gene deletions of NPHP1. Additionally, compound heterozygous mutations in NPHP3, NPHP4 and CEP164 were found in each one patient. The patients who had pathogenic mutations were significantly younger than those without mutations (median, 26 years old vs 68 years old, P = 0.045, Mann-Whitney U test), and no mutations in the known genes were detected in those aged ≥50 years (n = 9).

Conclusion

In the adult patients suspected of ciliopathy by renal biopsy, 29% were genetically diagnosed as nephronophthisis by our comprehensive genetic testing. Additionally, older patients tend not to have any pathogenic mutations in the known genes.

Funding

  • Government Support - Non-U.S.