Jiwon M Lee1, Young Seo Park2, Joo Hoon Lee2, Se Jin Park3, Jae Il Shin4, Yong-Hoon Park5, Kee Hwan Yoo6, Min Hyun Cho7, Su-Young Kim8, Seong Heon Kim8, Mee Kyung Namgoong9, Seung Joo Lee10, Jun Ho Lee11, Hee Yeon Cho12, Kyoung Hee Han13, Hee Gyung Kang1,14, Il Soo Ha1, Jun-Seok Bae15,16, Nayoung K D Kim15, Woong-Yang Park15,17, Hae Il Cheong1,14,18. 1. Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea. 2. Department of Pediatrics, Asan Medical Center, University of Ulsan, Seoul, Korea. 3. Department of Pediatrics, Ajou University School of Medicine, Suwon, Korea. 4. Department of Pediatrics, Severance Children's Hospital, Yonsei University, Seoul, Korea. 5. Department of Pediatrics, Yeungnam University College of Medicine, Daegu, Korea. 6. Department of Pediatrics, Korea University Guro Hospital, Seoul, Korea. 7. Department of Pediatrics, Kyungpook National University Hospital, Daegu, Korea. 8. Department of Pediatrics, Pusan National University Children's Hospital, Yangsan, Korea. 9. Department of Pediatrics, Wonju College of Medicine, Yonsei University, Wonju, Korea. 10. Department of Pediatrics, Ehwa University Mokdong Hospital, Seoul, Korea. 11. Department of Pediatrics, Bundang CHA Hospital, Seongnam, Korea. 12. Department of Pediatrics, Samsung Medical Center, Seoul, Korea. 13. Department of Pediatrics, Jeju University Hospital, Jeju, Korea. 14. Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, Korea. 15. Samsung Genome Institute, Samsung Medical Center, Seoul, Korea. 16. Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea. 17. Sungkyunkwan University School of Medicine, Seoul, Korea. 18. Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
Abstract
BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare disease with a genetic predisposition. Few studies have evaluated the disease in the Asian population. We studied a Korean pediatric cohort to delineate the clinical characteristics and genotypes. METHODS: A multicenter cohort of 51 Korean children with aHUS was screened for mutations using targeted exome sequencing covering 46 complement related genes. Anti-complement-factor-H autoantibody (anti-CFH) titers were measured. Multiplex ligation-dependent probe amplification assay was performed to detect deletions in the complement factor-H related protein genes (CFHR) in the patients as well as in 100 healthy Korean controls. We grouped the patients according to etiology and compared the clinical features using Mann-Whitney U-test and chi-squared test. RESULTS: Fifteen patients (group A, 29.7%) had anti-CFH, and mutations were detected in 11 (group B, 21.6%), including one with combined mutations. The remaining 25 (group C, 49.0%) were negative for both. The prevalence of anti-CFH was higher than the worldwide level. Group A had a higher onset age than group B, although the difference was not significant. Group B had the worst renal outcome. Gene frequencies of homozygous CFHR1 deletion were 73.3%, 2.7% and 1% in group A, group B + C and the control, respectively. CONCLUSIONS: The incidence of anti-CFH in the present Korean aHUS cohort was high. Clinical outcomes largely conformed to the previous reports. Although the sample size was limited, this cohort provides a reassessment of clinicogenetic features of aHUS in Korean children.
BACKGROUND:Atypical hemolytic uremic syndrome (aHUS) is a rare disease with a genetic predisposition. Few studies have evaluated the disease in the Asian population. We studied a Korean pediatric cohort to delineate the clinical characteristics and genotypes. METHODS: A multicenter cohort of 51 Korean children with aHUS was screened for mutations using targeted exome sequencing covering 46 complement related genes. Anti-complement-factor-H autoantibody (anti-CFH) titers were measured. Multiplex ligation-dependent probe amplification assay was performed to detect deletions in the complement factor-H related protein genes (CFHR) in the patients as well as in 100 healthy Korean controls. We grouped the patients according to etiology and compared the clinical features using Mann-Whitney U-test and chi-squared test. RESULTS: Fifteen patients (group A, 29.7%) had anti-CFH, and mutations were detected in 11 (group B, 21.6%), including one with combined mutations. The remaining 25 (group C, 49.0%) were negative for both. The prevalence of anti-CFH was higher than the worldwide level. Group A had a higher onset age than group B, although the difference was not significant. Group B had the worst renal outcome. Gene frequencies of homozygous CFHR1 deletion were 73.3%, 2.7% and 1% in group A, group B + C and the control, respectively. CONCLUSIONS: The incidence of anti-CFH in the present Korean aHUS cohort was high. Clinical outcomes largely conformed to the previous reports. Although the sample size was limited, this cohort provides a reassessment of clinicogenetic features of aHUS in Korean children.
Authors: Karolis Azukaitis; Eva Simkova; Mohammad Abdul Majid; Matthias Galiano; Kerstin Benz; Kerstin Amann; Clemens Bockmeyer; Radha Gajjar; Kevin E Meyers; Hae Il Cheong; Bärbel Lange-Sperandio; Therese Jungraithmayr; Véronique Frémeaux-Bacchi; Carsten Bergmann; Csaba Bereczki; Monika Miklaszewska; Dorottya Csuka; Zoltán Prohászka; Paul Killen; Patrick Gipson; Matthew G Sampson; Mathieu Lemaire; Franz Schaefer Journal: J Am Soc Nephrol Date: 2017-05-19 Impact factor: 14.978
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