Integration of exome sequencing and metabolic evaluation for the diagnosis of children with urolithiasis
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ORIGINAL ARTICLE
Integration of exome sequencing and metabolic evaluation for the diagnosis of children with urolithiasis Yining Zhao1 · Xiaoliang Fang1 · Yanjie Fan2 · Yu Sun2 · Lei He1 · Maosheng Xu1 · Guofeng Xu1 · Yufeng Li3 · Yunteng Huang4 · Yongguo Yu2 · Hongquan Geng1 Received: 1 November 2019 / Accepted: 7 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose To investigate the prevalence of inherited causes in an early onset urolithiasis cohort and each metabolic subgroup. Methods A retrospective analysis of both metabolic and genomic data was performed for the first 105 pediatric urolithiasis patients who underwent exome sequencing at our hospital from February 2016 to October 2018. Measurements included the diagnostic yield of exome sequencing in the entire cohort and each metabolic subgroup (hyperoxaluria, hypocitraturia, hypercalciuria, hyperuricosuria and cystine stone subgroups). The conformity between molecular diagnoses and metabolic evaluation was also evaluated. Results The present study involved a cohort of 105 pediatric patients with urolithiasis, from which diagnostic variants were identified in 38 patients (36%), including 27 primary hyperoxaluria and 11 cystinuria. In the metabolic subgroup analyses, 41% hyperoxaluria cases were primary hyperoxaluria caused by monogenic defects, and 100% of the causes of cystine stones could be explained by monogenic defects. However, no appropriate inherited causes were identified for hypocitraturia, hypercalciuria, or hyperuricosuria in the cohort. A high conformity (100%) was obtained between the molecular diagnoses and metabolic evaluation. Conclusion Exome sequencing in a cohort of 105 pediatric patients with urolithiasis yielded a genetic diagnosis in 36% of cases and the molecular diagnostic yield varies substantially across different metabolic abnormalities. Keywords Exome sequencing · Inherited disease · Metabolic evaluation · Pediatric urolithiasis
Introduction
Yining Zhao, Xiaoliang Fang, and Yanjie Fan contributed equally to this research as co-first authors. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00345-020-03449-9) contains supplementary material, which is available to authorized users. * Hongquan Geng [email protected] 1
Department of Pediatric Urology, Children’s Urolithiasis Treatment Center of National Health Commission of China, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai 200092, China
Department of Pediatric Endocrinology/Genetics, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China
2
Pediatric urolithiasis is an important problem in clinical pediatric urology practice. In China, urolithiasis affects approximately 0.27% of individuals aged younger than 20 years old [1]. Both genetic, metabolic, dietary, and anatomic factors can cause pediatric stone disease. According to the Online Mendelian Inheritance i
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