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07-12-2023 | Urolithiasis | Original Article

Beyond the kidney: extra-renal manifestations of monogenic nephrolithiasis and their significance

Authors: Chen-Han Wilfred Wu, Jad Badreddine, Ethan Su, Kimberly Tay, Hsin-Ti Cindy Lin, Stephen Rhodes, Fredrick Schumacher, Donald Bodner

Published in: Pediatric Nephrology | Issue 5/2024

Abstract

Background

The objective of this study was to explore the frequency of occurrence of extra-renal manifestations associated with monogenic nephrolithiasis.

Methods

A literature review was conducted to identify genes that are monogenic causes of nephrolithiasis. The Online Mendelian Inheritance in Man (OMIM) database was used to identify associated diseases and their properties. Disease phenotypes were ascertained using OMIM clinical synopses and sorted into 24 different phenotype categories as classified in OMIM. Disease phenotypes caused by the same gene were merged into a phenotypic profile of a gene (PPG) such that one PPG encompasses all related disease phenotypes for a specific gene. The total number of PPGs involving each phenotype category was measured, and the median phenotype category was determined. Phenotype categories were classified as overrepresented or underrepresented if the number of PPGs involving them was higher or lower than the median, respectively. Chi-square test was conducted to determine whether the number of PPGs affecting a given category significantly deviated from the median.

Results

Fifty-five genes were identified as monogenic causes of nephrolithiasis. A total of six significantly overrepresented and three significantly underrepresented phenotype categories were identified (p < 0.05). Four phenotypic categories (growth, neurological, skeletal, and abdomen/gastrointestinal) are significantly overrepresented after Bonferroni correction for multiple comparisons (p < 0.002). Among all phenotypes, impaired growth is the most common manifestation.

Conclusion

Recognizing the extra-renal manifestations associated with monogenic causes of kidney stones is critical for earlier diagnosis and optimal care in patients.

Graphical abstract

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Title: Beyond the kidney: extra-renal manifestations of monogenic nephrolithiasis and their significance
Authors: Chen-Han Wilfred Wu
Jad Badreddine
Ethan Su
Kimberly Tay
Hsin-Ti Cindy Lin
Stephen Rhodes
Fredrick Schumacher
Donald Bodner
Publication date: 07-12-2023
Publisher: Springer Berlin Heidelberg
Keyword: Urolithiasis
Published in: Pediatric Nephrology / Issue 5/2024
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI: https://doi.org/10.1007/s00467-023-06242-z

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Beyond the kidney: extra-renal manifestations of monogenic nephrolithiasis and their significance

Abstract

Background

Methods

Results

Conclusion

Graphical abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Graphical abstract

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