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.
CONCLUSIONS: Recognizing the extra-renal manifestations associated with monogenic causes of kidney stones is critical for earlier diagnosis and optimal care in patients.
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.
CONCLUSIONS: Recognizing the extra-renal manifestations associated with monogenic causes of kidney stones is critical for earlier diagnosis and optimal care in patients.
摘要：
背景：本研究的目的是探讨与单源性肾结石相关的肾外表现的发生频率。
方法：进行了文献综述，以确定肾结石的单基因原因。在线孟德尔人遗传（OMIM）数据库用于识别相关疾病及其特性。使用OMIM临床大纲确定疾病表型，并分为OMIM中分类的24种不同表型类别。将由相同基因引起的疾病表型合并到基因(PPG)的表型谱中,使得一个PPG涵盖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的总数，并确定了中位表型类别。如果涉及它们的PPG数量高于或低于中位数，则将表型类别分类为代表过多或代表不足。分别。进行卡方检验以确定影响给定类别的PPG的数量是否显著偏离中位数。
结果：55个基因被鉴定为肾结石的单基因原因。鉴定了总共六个显著过度代表和三个显著不足代表的表型类别(p<0.05)。四种表型类别(生长，神经学,骨骼，和腹部/胃肠道）在Bonferroni校正后进行多重比较（p<0.002）。在所有表型中，生长受损是最常见的表现。
结论：认识到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。更高分辨率版本的图形摘要可作为补充信息。
方法：进行了文献综述，以确定肾结石的单基因原因。在线孟德尔人遗传（OMIM）数据库用于识别相关疾病及其特性。使用OMIM临床大纲确定疾病表型，并分为OMIM中分类的24种不同表型类别。将由相同基因引起的疾病表型合并到基因(PPG)的表型谱中,使得一个PPG涵盖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的总数，并确定了中位表型类别。如果涉及它们的PPG数量高于或低于中位数，则将表型类别分类为代表过多或代表不足。分别。进行卡方检验以确定影响给定类别的PPG的数量是否显著偏离中位数。
结果：55个基因被鉴定为肾结石的单基因原因。鉴定了总共六个显著过度代表和三个显著不足代表的表型类别(p<0.05)。四种表型类别(生长，神经学,骨骼，和腹部/胃肠道）在Bonferroni校正后进行多重比较（p<0.002）。在所有表型中，生长受损是最常见的表现。
结论：认识到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。更高分辨率版本的图形摘要可作为补充信息。
