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dent_disease [2026/07/06 03:36] – [Other Findings] Scott Larsondent_disease [2026/07/06 03:37] (current) – Scott Larson
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 Dent disease is an **X-linked recessive** disorder caused by mutations in one of two genes: Dent disease is an **X-linked recessive** disorder caused by mutations in one of two genes:
  
-  * **Dent disease 1 (~60% of cases):** Caused by mutations in the **CLCN5** gene (chromosome Xp11.22), which encodes the electrogenic chloride/proton exchanger ClC-5. ClC-5 is predominantly expressed in the proximal tubule and controls acidification and recycling of endosomal compartments. Loss of ClC-5 function impairs megalin-mediated endocytic reabsorption of low-molecular-weight proteins.* +  * **Dent disease 1 (~60% of cases):** Caused by mutations in the **CLCN5** gene (chromosome Xp11.22), which encodes the electrogenic chloride/proton exchanger ClC-5. ClC-5 is predominantly expressed in the proximal tubule and controls acidification and recycling of endosomal compartments. Loss of ClC-5 function impairs megalin-mediated endocytic reabsorption of low-molecular-weight proteins. 
-  * **Dent disease 2 (~15% of cases):** Caused by mutations in the **OCRL** gene (chromosome Xq25), which encodes a phosphatidylinositol-4,5-bisphosphate 5-phosphatase (OCRL1). OCRL mutations are also responsible for Lowe syndrome; Dent disease 2 is considered a milder phenotypic variant. Both ClC-5 and OCRL1 participate in a common endocytic pathway in the proximal tubule.* +  * **Dent disease 2 (~15% of cases):** Caused by mutations in the **OCRL** gene (chromosome Xq25), which encodes a phosphatidylinositol-4,5-bisphosphate 5-phosphatase (OCRL1). OCRL mutations are also responsible for Lowe syndrome; Dent disease 2 is considered a milder phenotypic variant. Both ClC-5 and OCRL1 participate in a common endocytic pathway in the proximal tubule. 
-  * **Remaining ~25% of cases:** The genetic cause is unknown, suggesting involvement of additional genes.*+  * **Remaining ~25% of cases:** The genetic cause is unknown, suggesting involvement of additional genes.
  
 There is considerable intra-familial variability in disease severity, and no clear genotype-phenotype correlation has been established, although mutations affecting the pore or CBS domains of ClC-5 may be associated with more frequent GFR decline. There is considerable intra-familial variability in disease severity, and no clear genotype-phenotype correlation has been established, although mutations affecting the pore or CBS domains of ClC-5 may be associated with more frequent GFR decline.
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   - MedlinePlus. Dent disease. National Library of Medicine. [[https://medlineplus.gov/genetics/condition/dent-disease/]]   - MedlinePlus. Dent disease. National Library of Medicine. [[https://medlineplus.gov/genetics/condition/dent-disease/]]
  
 +{{tag>syndrome}}