Abstract: FR-PO329

Genomic Background of Adult Polycystic Kidney Disease Patients without a Family History

Session Information

Category: Genetic Diseases of the Kidney

  • 801 Cystic Kidney Diseases

Authors

  • Fujimaru, Takuya, 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
  • 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
  • Mori, Takayasu, Tokyo Medical and Dental University, Tokyo, Japan
  • Sekine, Akinari, Toranomon Hospital, 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
  • Nomura, Naohiro, Tokyo Medical and Dental University, Tokyo, Japan
Background

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. Mutations in PKD1 and PKD2 are responsible for 85% and 15% of ADPKD patients, respectively. Diagnosis of ADPKD is usually based on positive family history and imaging findings. However, in the absence of a family history, there are no definitive imaging findings that provide an unequivocal diagnosis of ADPKD. Therefore, in the patients without a family history, it is required to distinguish ADPKD from other polycystic kidney diseases (PKDs), though it is difficult without genetic diagnosis in most of the cases.

Methods

We developed a custom panel for 69 genes that cause nine types of hereditary PKDs (ADPKD, autosomal recessive polycystic kidney disease, nephronophthisis, Joubert syndrome, Meckel syndrome, Senior-Loken syndrome, Bardet-Biedl syndrome, etc.) using next-generation sequencing. Comprehensive genetic screening approach was performed for the adult PKD patients without a family history. PKD was defined as more than 10 cysts in a kidney.

Results

Through the analysis for 35 patients (age 55±16, 68.6% of male), 19 patients (54.3%) had PKD1/PKD2 mutations. Two patients (5.7%) identified compound heterozygous mutations in other genes, PKHD1 and NPHP4, confirmed by trio analysis. De novo heterozygous frameshift mutation of OFD1 was identified in one patient, which was likely to be causal. No obvious responsible mutations were detected in remaining 13 patients (37.1%).

Conclusion

In the adult PKD patients without a family history, other cystic kidney diseases than ADPKD may be overlooked, although it is hard to distinguish only by clinical data. Our custom panel appears to be useful to make genetic diagnosis of these patients.

Funding

  • Government Support - Non-U.S.