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Abstract: TH-PO819

Clinical and Genetic Characteristics in Dent Disease 2 and Lowe Syndrome

Session Information

Category: Genetic Diseases of the Kidneys

  • 1002 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • Sakakibara, Nana, Kobe University Graduate School of Medicine, Kobe, Japan
  • Nozu, Kandai, Kobe University Graduate School of Medicine, Kobe, Japan
  • Nagano, China, Kobe University Graduate School of Medicine, Kobe, Japan
  • Horinouchi, Tomoko, Kobe University Graduate School of Medicine, Kobe, Japan
  • Yamamura, Tomohiko, Kobe University Graduate School of Medicine, Kobe, Japan
  • Shima, Yuko, Wakayama Medical University, Wakayama City, Japan
  • Nakanishi, Koichi, Graduate School of Medicine, University of the Ryukyus, Nishihara-cho, Japan
  • Iijima, Kazumoto, Kobe University Graduate School of Medicine, Kobe, Japan

Group or Team Name

  • Department of pediatrics
Background

Dent disease is associated with low molecular weight proteinuria and hypercalciuria and caused by mutations in either two genes of CLCN5 (Dent disease 1) or OCRL (Dent disease 2). On the other hand, Lowe syndrome is characterized by congenital cataract, developmental delay and Fanconi syndrome. Lowe syndrome is also caused by OCRL gene mutations, but the clinical severity differs between these two diseases. The reason for this difference remains unclear, but previous reports have shown that patients with any type of mutations before exon 7 were diagnosed with Dent disease, and those with truncating mutations after exon 8 were diagnosed with Lowe syndrome. The purpose of this study is to investigate the difference in clinical and genetic characters between Dent disease 2 and Lowe syndrome in the Japanese population.

Methods

We conducted gene test for clinically suspected cases of Dent disease or Lowe syndrome. In total, 22 male cases in 20 families were detected the mutations in OCRL gene. We retrospectively studied these patients to investigate the genotype-phenotype correlation in OCRL disorders.

Results


Eleven patients were clinically diagnosed with Lowe syndrome and 11 patients in 9 families with Dent disease 2. Seven novel mutations were identified. Four cases had mutations before exon 7, all of which were Dent disease 2. All patients who had truncating mutations or large deletions after exon 8 were diagnosed with Lowe syndrome, whereas missense mutations after exon 8 were associated with both Lowe syndrome and Dent disease 2. In other words, all cases of Dent disease 2 with mutations after exon 8 had missense mutations. Four of the patients diagnosed with Lowe syndrome were able to walk independently. Of these four cases, two had missense mutations and the other two had splice-site mutations.

Conclusion

As in previous reports, all patients with any type of mutations before OCRL exon 7 were Dent disease 2, and truncating mutation after exon 8 were Lowe syndrome. However, missense and splice-site mutations after exon 8 showed a spectrum ranging from Dent disease 2 to relatively mild Lowe syndrome.