Yining Zhao1, Xiaoliang Fang1, Yanjie Fan2, Yu Sun2, Lei He1, Maosheng Xu1, Guofeng Xu1, Yufeng Li3, Yunteng Huang4, Yongguo Yu2, Hongquan Geng5. 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. 2. Department of Pediatric Endocrinology/Genetics, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China. 3. Department of Pediatric Nephrology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China. 4. Department of Urology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China. 5. 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. genghongquan@xinhuamed.com.cn.
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.
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.
Authors: Katharina Hopp; Andrea G Cogal; Eric J Bergstralh; Barbara M Seide; Julie B Olson; Alicia M Meek; John C Lieske; Dawn S Milliner; Peter C Harris Journal: J Am Soc Nephrol Date: 2015-02-02 Impact factor: 10.121
Authors: Ankana Daga; Amar J Majmundar; Daniela A Braun; Heon Yung Gee; Jennifer A Lawson; Shirlee Shril; Tilman Jobst-Schwan; Asaf Vivante; David Schapiro; Weizhen Tan; Jillian K Warejko; Eugen Widmeier; Caleb P Nelson; Hanan M Fathy; Zoran Gucev; Neveen A Soliman; Seema Hashmi; Jan Halbritter; Margarita Halty; Jameela A Kari; Sherif El-Desoky; Michael A Ferguson; Michael J G Somers; Avram Z Traum; Deborah R Stein; Ghaleb H Daouk; Nancy M Rodig; Avi Katz; Christian Hanna; Andrew L Schwaderer; John A Sayer; Ari J Wassner; Shrikant Mane; Richard P Lifton; Danko Milosevic; Velibor Tasic; Michelle A Baum; Friedhelm Hildebrandt Journal: Kidney Int Date: 2017-10-12 Impact factor: 10.612