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Kidney Week

Abstract: SA-PO775

Monoallelic IFT140 Pathogenic Variants in Adult Polycystic Kidney Disease Patients Without Family History

Session Information

Category: Genetic Diseases of the Kidneys

  • 1201 Genetic Diseases of the Kidneys: Cystic

Authors

  • Fujimaru, Takuya, Tokyo Medical and Dental University, Tokyo, Japan
  • Mori, Takayasu, Tokyo Medical and Dental University, Tokyo, Japan
  • Chiga, Motoko, Tokyo Medical and Dental University, Tokyo, Japan
  • Mandai, Shintaro, Tokyo Medical and Dental University, Tokyo, Japan
  • Hara, Yu, Tokyo Medical and Dental University, Tokyo, Japan
  • Fujiki, Tamami, Tokyo Medical and Dental University, Tokyo, Japan
  • Kikuchi, Hiroaki, Tokyo Medical and Dental University, Tokyo, Japan
  • Mori, Yutaro, Tokyo Medical and Dental University, Tokyo, Japan
  • Ando, Fumiaki, Tokyo Medical and Dental University, Tokyo, Japan
  • Susa, Koichiro, Tokyo Medical and Dental University, Tokyo, Japan
  • Iimori, Soichiro, Tokyo Medical and Dental University, Tokyo, Japan
  • Naito, Shotaro, Tokyo Medical and Dental University, Tokyo, Japan
  • Uchida, Shinichi, Tokyo Medical and Dental University, Tokyo, Japan
  • Sohara, Eisei, Tokyo Medical and Dental University, Tokyo, Japan
Background

IFT140 encodes a subunit of intraflagellar transport complex A, which is involved in retrograde ciliary transport. IFT140 is known as a causative gene of Meinzer-Sardino syndrome, an autosomal recessive ciliopathy that presents with short-costothoracic dysplasia. Recently, heterozygous variants in IFT140 were reported to cause autosomal dominant polycystic kidney disease (ADPKD). We investigated the presence of IFT140 pathogenic variants in patients with polycystic kidney disease without family history.

Methods

We performed a comprehensive genetic analysis in 151 adult polycystic kidney patients without family history. Targeted genes were 69-92 genes including IFT140 responsible for 6 hereditary cystic kidney diseases (ADPKD, autosomal recessive polycystic kidney disease, nephronophthisis, nephronophthisis-related ciliopathies, autosomal dominant tubular interstitial kidney disease, and autosomal dominant polycystic liver disease).

Results

Through this analysis, 50 patients (33%) had pathogenic variants in PKD1 or PKD2 genes. Additionally, 4 patients had pathogenic variants in other genes (HNF1B, n = 2; OFD1, n = 1, PKHD1, n = 1). In 6 of 97 patients (6%) who did not have any apparent pathogenic variant in known causative genes, heterozygous pathogenic variants were detected in IFT140 gene (frameshift variant, n = 3; nonsense variant, n = 2; splicing variant, n = 1). None of the patients with heterozygous pathogenic variants in IFT140 had liver cysts. Additionally, although total kidney volume were large (median, 1357 ml), renal cysts were asymmetric and atypical. Furthermore, the patients with IFT140 pathogenic variants were older (median, 59.5 years old) and had better renal function (median eGFR, 57.2 ml/min/1.73m2) at the time of genetic analysis.

Conclusion

IFT140 should be considered as the responsible gene for polycystic kidney disease, even in the patients had no family history.

Funding

  • Government Support – Non-U.S.