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A Scalable, Cell-Based Method for the Functional Assessment of Ube3a Variants
Published on: October 10, 2022
Clinical and functional characterization of URAT1 variants
Velibor Tasic1, Ann Marie Hynes, Kenichiro Kitamura
1Medical School, University Children's Hospital, Skopje, Macedonia.
Plos One
|December 24, 2011
Summary
Idiopathic renal hypouricaemia, caused by mutations in the URAT1 gene, leads to excessive uric acid loss and kidney problems. Identifying these genetic mutations is key for diagnosing and managing related renal symptoms.
Area of Science:
- Nephrology
- Human Genetics
- Molecular Biology
Background:
- Idiopathic renal hypouricaemia is an inherited disorder characterized by excessive urinary uric acid excretion.
- This condition can lead to renal complications such as kidney stones, hematuria, pyelonephritis, and nephrocalcinosis.
- Hypouricaemia may also present as exercise-induced acute kidney injury.
Purpose of the Study:
- To investigate the genetic basis of idiopathic renal hypouricaemia in Macedonian and British patients.
- To correlate identified genetic mutations with functional changes in urate transport.
- To emphasize the role of the URAT1 transporter in serum urate homeostasis and associated renal phenotypes.
Main Methods:
- Genetic analysis to identify mutations in the SLC22A12 gene, which encodes URAT1.
- Functional characterization of urate transport using uptake experiments in HEK293 cells.
- Clinical correlation of genetic findings with patient renal symptoms and signs.
Main Results:
- Heterozygous missense mutations in SLC22A12 were identified in patients with hypouricaemia.
- Functional studies confirmed that these mutations impair urate transporter activity.
- The identified mutations were linked to various renal manifestations, including renal stone disease.
Conclusions:
- The URAT1 renal urate transporter is crucial for maintaining serum urate levels.
- Mutations in SLC22A12 causing impaired URAT1 function are a significant cause of inherited renal hypouricaemia.
- Clinicians should consider inherited renal hypouricaemia in patients presenting with nephrolithiasis and other renal abnormalities.
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