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Abstract: PO1324

Examination of the Predicted Prevalence of Gitelman Syndrome by Ethnicity Based on Genome Databases

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Kondo, Atsushi, Kobe University Graduate School of Medicine, Department of Pediatrics, Kobe, Hyogo, Japan
  • Nagai, Sadayuki, Kobe University Graduate School of Medicine, Department of Pediatrics, Kobe, Hyogo, Japan
  • Aoto, Yuya, Kobe University Graduate School of Medicine, Department of Pediatrics, Kobe, Hyogo, Japan
  • Sakakibara, Nana, Kobe University Graduate School of Medicine, Department of Pediatrics, Kobe, Hyogo, Japan
  • Nagano, China, Kobe University Graduate School of Medicine, Department of Pediatrics, Kobe, Hyogo, Japan
  • Horinouchi, Tomoko, Kobe University Graduate School of Medicine, Department of Pediatrics, Kobe, Hyogo, Japan
  • Yamamura, Tomohiko, Kobe University Graduate School of Medicine, Department of Pediatrics, Kobe, Hyogo, Japan
  • Iijima, Kazumoto, Hyogo Prefectural Kobe Children’s Hospital, Kobe, Hyogo, Japan
  • Nozu, Kandai, Kobe University Graduate School of Medicine, Department of Pediatrics, Kobe, Hyogo, Japan
Background

Gitelman syndrome is an autosomal recessive inherited salt-losing tubulopathy. It has a prevalence of around 1 in 40,000 people, and heterozygous carriers are estimated at approximately 1%, although the exact prevalence is unknown because most cases are thought to be asymptomatic or have nonspecific clinical findings. On the other hand, it has been reported that the non-specific symptoms can reduce the quality of life of patients, and in practice, we have often experienced cases where patients have suffered from these symptoms since childhood, but were not diagnosed and therefore not treated, and were diagnosed in adulthood. It could suggest that there are far more patients and carriers than expected.

Methods

We estimated the predicted prevalence of Gitelman syndrome based on multiple genome databases, HGVD and jMorp for the Japanese population and gnomAD for other ethnicities, and included all 274 pathogenic missense or nonsense mutations registered in HGMD Professional. The frequencies of all these alleles were summed to calculate the total variant allele frequency in SLC12A3 which is the responsible gene for Gitelman syndrome. The carrier frequency and the disease prevalence were assumed to be twice and the square of the total allele frequency, respectively, according to the Hardy–Weinberg principle.

Results

In the Japanese population, the total carrier frequencies were 0.0948 (9.5%) and 0.0868 (8.7%) and the calculated prevalence was 0.00225 (2.3 in 1000 people) and 0.00188 (1.9 in 1000 people) in HGVD and jMorp, respectively. Other ethnicities showed a prevalence varying from 0.000012 to 0.00083.

Conclusion

These findings indicate that the prevalence of Gitelman syndrome in the Japanese population is higher than expected and that some other ethnicities also have a higher prevalence than previously been considered.