Fang Wang1, Yanqin Zhang1, Jianhua Mao2, Zihua Yu3, Zhuwen Yi4, Li Yu5, Jun Sun6,7, Xiuxiu Wei6,7, Fangrui Ding1, Hongwen Zhang1, Huijie Xiao1, Yong Yao1, Weizhen Tan8, Svjetlana Lovric8, Jie Ding9, Friedhelm Hildebrandt10. 1. Department of Pediatrics, Peking University First Hospital, No. 1, Xi An Men Da Jie, Beijing, 100034, People's Republic of China. 2. Department of Nephrology, The Children Hospital of Zhejiang University School of Medicine, Hangzhou, People's Republic of China. 3. Department of Pediatrics, Fuzhou Dongfang Hospital, Fuzhou, People's Republic of China. 4. Department of Pediatrics, The Second Xiangya Hospital, Central South University, Changsha, People's Republic of China. 5. Department of Pediatrics, Guangzhou First People's Hospital, Guangzhou, People's Republic of China. 6. Binhai Genomics Institute, Tianjin Translational Genomics Center, BGI-Tianjin, BGI-shenzhen, Tianjin, People's Republic of China. 7. BGI-Shenzhen, Shenzhen, People's Republic of China. 8. Division of Nephrology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Enders 561, Boston, MA, 02115, USA. 9. Department of Pediatrics, Peking University First Hospital, No. 1, Xi An Men Da Jie, Beijing, 100034, People's Republic of China. djnc_5855@126.com. 10. Division of Nephrology, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Enders 561, Boston, MA, 02115, USA. friedhelm.hildebrandt@childrens.harvard.edu.
Abstract
BACKGROUND: The aim of this study was to elucidate whether genetic screening test results of pediatric patients with steroid-resistant nephrotic syndrome (SRNS) vary with ethnicity. METHODS: Using high-throughput DNA sequencing, 28 nephrotic syndrome-related genes were analyzed in 110 chil-dren affected by SRNS and 10 children with isolated proteinuria enrolled by 5 centers in China (67 boys, 53 girls). Their age at disease onset ranged from 1 day to 208 months (median, 48.8 months). Patients were excluded if their age at onset of disease was over 18 years or if they were diagnosed as having Alport syndrome. RESULTS: A genetic etiology was identified in 28.3% of our cohort and the likelihood of establishing a genetic diagnosis decreased as the age at onset of nephrotic syndrome increased. The most common mutated genes were ADCK4 (6.67%), NPHS1 (5.83%), WT1 (5.83%), and NPHS2 (3.33%), and the difference in the frequencies of ADCK4 and NPHS2 mutations between this study and a study on monogenic causes of SRNS in the largest international cohort of 1,783 different families was significant. A case of congenital nephrotic syndrome was attributed to a homozygous missense mutation in ADCK4, and a de novo missense mutation in TRPC6 was detected in a case of infantile nephrotic syndrome. CONCLUSIONS: Our results showed that, in the first and the largest multicenter cohort of Chinese pediatric SRNS reported to date, ADCK4 is the most common causative gene, whereas there is a low prevalence of NPHS2 mutations. Our data indicated that the genetic testing results for pediatric SRNS patients vary with different ethnicities, and this information will help to improve management of the disease in clinical practice.
BACKGROUND: The aim of this study was to elucidate whether genetic screening test results of pediatric patients with steroid-resistant nephrotic syndrome (SRNS) vary with ethnicity. METHODS: Using high-throughput DNA sequencing, 28 nephrotic syndrome-related genes were analyzed in 110 chil-dren affected by SRNS and 10 children with isolated proteinuria enrolled by 5 centers in China (67 boys, 53 girls). Their age at disease onset ranged from 1 day to 208 months (median, 48.8 months). Patients were excluded if their age at onset of disease was over 18 years or if they were diagnosed as having Alport syndrome. RESULTS: A genetic etiology was identified in 28.3% of our cohort and the likelihood of establishing a genetic diagnosis decreased as the age at onset of nephrotic syndrome increased. The most common mutated genes were ADCK4 (6.67%), NPHS1 (5.83%), WT1 (5.83%), and NPHS2 (3.33%), and the difference in the frequencies of ADCK4 and NPHS2 mutations between this study and a study on monogenic causes of SRNS in the largest international cohort of 1,783 different families was significant. A case of congenital nephrotic syndrome was attributed to a homozygous missense mutation in ADCK4, and a de novo missense mutation in TRPC6 was detected in a case of infantile nephrotic syndrome. CONCLUSIONS: Our results showed that, in the first and the largest multicenter cohort of Chinese pediatric SRNS reported to date, ADCK4 is the most common causative gene, whereas there is a low prevalence of NPHS2 mutations. Our data indicated that the genetic testing results for pediatric SRNS patients vary with different ethnicities, and this information will help to improve management of the disease in clinical practice.
Authors: Agnes Trautmann; Monica Bodria; Fatih Ozaltin; Alaleh Gheisari; Anette Melk; Marta Azocar; Ali Anarat; Salim Caliskan; Francesco Emma; Jutta Gellermann; Jun Oh; Esra Baskin; Joanna Ksiazek; Giuseppe Remuzzi; Ozlem Erdogan; Sema Akman; Jiri Dusek; Tinatin Davitaia; Ozan Özkaya; Fotios Papachristou; Agnieszka Firszt-Adamczyk; Tomasz Urasinski; Sara Testa; Rafael T Krmar; Lidia Hyla-Klekot; Andrea Pasini; Z Birsin Özcakar; Peter Sallay; Nilgun Cakar; Monica Galanti; Joelle Terzic; Bilal Aoun; Alberto Caldas Afonso; Hanna Szymanik-Grzelak; Beata S Lipska; Sven Schnaidt; Franz Schaefer Journal: Clin J Am Soc Nephrol Date: 2015-01-29 Impact factor: 8.237
Authors: N Boute; O Gribouval; S Roselli; F Benessy; H Lee; A Fuchshuber; K Dahan; M C Gubler; P Niaudet; C Antignac Journal: Nat Genet Date: 2000-04 Impact factor: 38.330
Authors: Jung Sue Kim; Christine A Bellew; Douglas M Silverstein; Diego H Aviles; Frank G Boineau; V Matti Vehaskari Journal: Kidney Int Date: 2005-09 Impact factor: 10.612
Authors: Michael Schultheiss; Rainer G Ruf; Bettina E Mucha; Roger Wiggins; Arno Fuchshuber; Anne Lichtenberger; Friedhelm Hildebrandt Journal: Pediatr Nephrol Date: 2004-12 Impact factor: 3.714
Authors: Gil Chernin; Saskia F Heeringa; Rasheed Gbadegesin; Jinhong Liu; Bernward G Hinkes; Christopher N Vlangos; Virginia Vega-Warner; Friedhelm Hildebrandt Journal: Pediatr Nephrol Date: 2008-06-10 Impact factor: 3.714