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

中文翻译：

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肾脏之外：单基因肾结石的肾外表现及其意义

背景

本研究的目的是探讨与单基因肾结石相关的肾外表现的发生频率。

方法

进行文献综述以确定肾结石单基因原因的基因。人类在线孟德尔遗传 (OMIM) 数据库用于识别相关疾病及其特性。使用 OMIM 临床概要确定疾病表型，并将其分为 OMIM 中分类的 24 种不同表型类别。由同一基因引起的疾病表型被合并到基因表型谱（PPG）中，这样一个PPG涵盖了特定基因的所有相关疾病表型。测量涉及每个表型类别的 PPG 总数，并确定中位表型类别。如果涉及表型类别的 PPG 数量分别高于或低于中位数，则表型类别被分类为代表性过高或代表性不足。进行卡方检验以确定影响给定类别的 PPG 数量是否显着偏离中位数。

结果

55 个基因被确定为肾结石的单基因原因。总共确定了六个显着过高和三个显着不足的表型类别（p  < 0.05）。经过 Bonferroni 校正进行多重比较后，四种表型类别（生长、神经、骨骼和腹部/胃肠道）显着过高 ( p  < 0.002)。在所有表型中，生长受损是最常见的表现。

结论

认识与肾结石的单基因原因相关的肾外表现对于患者的早期诊断和最佳护理至关重要。

图形概要