The objective of this study was to explore the frequency of occurrence of extra-renal manifestations associated with monogenic nephrolithiasis.
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.
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.
Recognizing the extra-renal manifestations associated with monogenic causes of kidney stones is critical for earlier diagnosis and optimal care in patients. A higher resolution version of the Graphical abstract is available as Supplementary information.
Pediatric nephrology (Berlin, Germany). 2023 Dec 07 [Epub ahead of print]
Chen-Han Wilfred Wu, Jad Badreddine, Ethan Su, Kimberly Tay, Hsin-Ti Cindy Lin, Stephen Rhodes, Fredrick Schumacher, Donald Bodner
Department of Urology, Case Western Reserve University School of Medicine and University Hospitals, 11100 Euclid Ave., Cleveland, OH, 44106, USA. ., Department of Urology, Case Western Reserve University School of Medicine and University Hospitals, 11100 Euclid Ave., Cleveland, OH, 44106, USA., Department of Population and Quantitative Health Sciences, School of Medicine, Cleveland, OH, USA.