ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Abstract: SA-PO767

Discovery of a Novel Candidate Gene Implicated in X-Linked Polycystic Kidney Disease

Session Information

Category: Genetic Diseases of the Kidneys

  • 1201 Genetic Diseases of the Kidneys: Cystic

Authors

  • Mori, Takayasu, Department of Nephrology, Tokyo Medical and Dental Sciences, Tokyo, Japan, Bunkyo-ku, Tokyo, Japan
  • Fujimaru, Takuya, Department of Nephrology, Tokyo Medical and Dental Sciences, Tokyo, Japan, Bunkyo-ku, Tokyo, Japan
  • Liu, Chunyu, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, Shanghai, China
  • Patterson, Karynne, University of Washington, Seattle, Washington, United States
  • Yamamoto, Kohei, Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan
  • Suzuki, Takefumi, Department of Nephrology, Tokyo Medical and Dental Sciences, Tokyo, Japan, Bunkyo-ku, Tokyo, Japan
  • Chiga, Motoko, Department of Nephrology, Tokyo Medical and Dental Sciences, Tokyo, Japan, Bunkyo-ku, Tokyo, Japan
  • Mandai, Shintaro, Department of Nephrology, Tokyo Medical and Dental Sciences, Tokyo, Japan, Bunkyo-ku, Tokyo, Japan
  • Ando, Fumiaki, Department of Nephrology, Tokyo Medical and Dental Sciences, Tokyo, Japan, Bunkyo-ku, Tokyo, Japan
  • Mori, Yutaro, Department of Nephrology, Tokyo Medical and Dental Sciences, Tokyo, Japan, Bunkyo-ku, Tokyo, Japan
  • Susa, Koichiro, Department of Nephrology, Tokyo Medical and Dental Sciences, Tokyo, Japan, Bunkyo-ku, Tokyo, Japan
  • Tan, Yue-Qiu, Institute of Reproductive and Stem Cell Engineering, NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Science, Central South University, Changsha, Changsha , China
  • Zhang, Feng, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, Shanghai, China
  • Uchida, Shinichi, Department of Nephrology, Tokyo Medical and Dental Sciences, Tokyo, Japan, Bunkyo-ku, Tokyo, Japan
  • Sohara, Eisei, Department of Nephrology, Tokyo Medical and Dental Sciences, Tokyo, Japan, Bunkyo-ku, Tokyo, Japan

Group or Team Name

  • University of Washington Center for Rare Disease Research.
Background

Autosomal dominant polycystic kidney disease (ADPKD) is characterized by typical imaging findings and a family history and ~90% of cases have a genetic explanation. In contrast, the underlying genetic basis of adult-onset sporadic cystic kidney disease remains incompletely elucidated, with ~30% of patients in our cohort remaining unexplained by variants in established cyst-related genes, leading to inconclusive diagnoses. These individuals were presumed to harbor potentially unreported mutations in novel candidate genes associated with PKD.

Methods

An NGS panel screening was conducted to analyze 69 known genes associated with renal cysts in adult patients with no familial history of the condition. Whole genome sequencing was performed on 47 unrelated individuals who did not exhibit any pathogenic candidate variants, aiming to identify novel genes implicated in renal cyst formation.

Results

Candidate gene A, located on the X chromosome, exhibited missense variants found in three male patients aged 74 (PT570), 80 (PT698), and 58 (PT1216) years, respectively. These patients demonstrated renal function impairment with estimated glomerular filtration rates (eGFR) of 53.5, 21.8, and 20.2 ml/min/1.73m2, respectively. Hypertension was a shared characteristic among all patients, while no complications associated with hepatic cysts were observed. The protein product of gene A was found to be expressed in the primary cilia of human renal tubules. Kidneys from 12-month-old male knockout mice lacking gene A exhibited vacuolation of tubular cells and tubular dilation, providing evidence that gene A is a novel causative gene involved in cyst formation.

Conclusion

Gene A is a newly discovered gene associated with PKD, demonstrating X-linked inheritance, which is uncommon in inherited cases of PKD. Further accumulation of cases is warranted for a more comprehensive understanding.

Funding

  • Government Support – Non-U.S.