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Abstract: SA-PO574

Clinical Characterization of a Dent Disease-1 Cohort Including Genotype-Phenotype Correlations

Session Information

  • Genetic Diseases: Diagnosis
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

  • 1102 Genetic Diseases of the Kidneys: Non-Cystic


  • Arnous, Muhammad G., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Cogal, Andrea G., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Arroyo, Jennifer, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Anglani, Franca, Universita degli Studi di Padova, Padova, Veneto, Italy
  • Harris, Peter C., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Lieske, John C., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Dent disease is an X-linked recessive renal disorder associated with Low molecular weight proteinuria, kidney stones, nephrocalcinosis, and kidney failure in the 3rd to 5th decade. Dent-1 is caused by mutations in the CLCN5 gene and Dent-2 mutations in the OCRL2 gene. DD-1 accounts for 60% of diagnosed patients


Review of 134 patients from (RKSC) DD Registry (65 unique mutations). CLCN5 variants were assessed for pathogenicity using ACMG guidelines and categorized as truncating (nonsense, frameshift, large deletions, and canonical splice-site mutations) and nontruncating (missense and non-frame mutations). Correlations were analyzed using observational statistics and survival analysis methods.


Missense mutations were the most prevalent (37%), followed by frameshift (23%) and nonsense (23%). Overall truncating (65%) were more common than non-truncating (35%) mutations. Patients with truncating mutations had more prevalent nephrocalcinosis, experienced stone events earlier in life, and manifested a higher albumin excretion rate than the non-truncating group.
Patients with non-truncating mutations developed hematuria more often. No statistically significant difference between the 2 groups regarding CKD evolution.
24h urine Ca was positively associated with lifetime stone events and CKD evolution among the whole cohort. 24h urine protein was positively associated with CKD evolution but not associated with nephrolithiasis. Stratifying the cohort by mutation type, Lifetime stone events positively correlated with CKD evolution within the truncating group.


DD-1 patients with truncating mutations tended to have a more severe disease course compared to those with non-truncating mutations. Functional studies of the effect of specific mutations on intracellular processes and function, and overall renal physiology, may help to elucidate the underlying reasons.

Genotype-phenotype correlations
Patients' category
Total N:134
Prevalent nephrocalcinosis66%50%0.031
Age at 1st stone event14(10-20)27(21-27)0.014
Total Urine Protein
Urine Albumin (mg/24h urine)180.6 (119.15-279.5)106.6 (74.45-176.95)0.019
LMWP: alpha-1mg/24h502.5 (321.5-602)157 (71-522)0.268


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