Eujin Park1, Yo Han Ahn1, Hee Gyung Kang1,2, Noriko Miyake3, Hiroyasu Tsukaguchi4, Hae Il Cheong1,2,5. 1. Department of Pediatrics, Seoul National University Children's Hospital, Seoul, Korea. 2. Research Coordination Center for Rare Diseases, Seoul National University Hospital, Seoul, Korea. 3. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan. 4. Second Department of Internal Medicine, Kansai Medical University, Osaka, Japan. 5. Kidney Research Institute, Medical Research Center, Seoul National University College of Medicine, Seoul, Korea.
Abstract
BACKGROUND: NUP107 is a novel gene associated with autosomal recessive steroid-resistant nephrotic syndrome (SRNS) with focal segmental glomerulosclerosis (FSGS) in children. The frequency of NUP107 mutations in children with SR-FSGS remains unknown. METHODS: Nine families with two siblings affected by childhood-onset SRNS or proteinuria were recruited. FSGS was confirmed by a kidney biopsy in at least one affected sibling in all families. Additionally, 69 sporadic pediatric cases with biopsy-proven SR-FSGS who had not responded to any treatment were included. All coding exons with flanking introns of the NUP107 gene were amplified using polymerase chain reaction and directly sequenced. RESULTS: Biallelic NUP107 mutations were detected in four pairs (44.4%) of siblings from the familial cases and three (4.3%) sporadic cases. All affected patients harbored the p.Asp831Ala mutation in one allele and a truncating or abnormal splicing mutation in the other allele. NUP107 mutation-positive patients showed an earlier onset age (39.4 ± 13.1 versus 76.8 ± 50.0 months, P= 0.027) and more rapid progression to end-stage renal disease (at the ages of 58.9 ± 23.4 versus 123.1 ± 62.7 months, P < 0.001) compared with mutation-negative patients. None of the eight mutation-positive cases, who underwent kidney transplantation, showed recurrence of FSGS in the graft kidney, while 35.3% of mutation-negative cases showed recurrence of FSGS. CONCLUSIONS: An unexpectedly high incidence of NUP107 mutations was observed in Korean children with SR-FSGS. Initial genetic screening of children with SR-FSGS should include the NUP107 gene, at least in Korea. Further studies are necessary to determine the incidences of NUP107 mutations in other countries.
BACKGROUND: NUP107 is a novel gene associated with autosomal recessive steroid-resistant nephrotic syndrome (SRNS) with focal segmental glomerulosclerosis (FSGS) in children. The frequency of NUP107 mutations in children with SR-FSGS remains unknown. METHODS: Nine families with two siblings affected by childhood-onset SRNS or proteinuria were recruited. FSGS was confirmed by a kidney biopsy in at least one affected sibling in all families. Additionally, 69 sporadic pediatric cases with biopsy-proven SR-FSGS who had not responded to any treatment were included. All coding exons with flanking introns of the NUP107 gene were amplified using polymerase chain reaction and directly sequenced. RESULTS: Biallelic NUP107 mutations were detected in four pairs (44.4%) of siblings from the familial cases and three (4.3%) sporadic cases. All affected patients harbored the p.Asp831Ala mutation in one allele and a truncating or abnormal splicing mutation in the other allele. NUP107 mutation-positive patients showed an earlier onset age (39.4 ± 13.1 versus 76.8 ± 50.0 months, P= 0.027) and more rapid progression to end-stage renal disease (at the ages of 58.9 ± 23.4 versus 123.1 ± 62.7 months, P < 0.001) compared with mutation-negative patients. None of the eight mutation-positive cases, who underwent kidney transplantation, showed recurrence of FSGS in the graft kidney, while 35.3% of mutation-negative cases showed recurrence of FSGS. CONCLUSIONS: An unexpectedly high incidence of NUP107 mutations was observed in Korean children with SR-FSGS. Initial genetic screening of children with SR-FSGS should include the NUP107 gene, at least in Korea. Further studies are necessary to determine the incidences of NUP107 mutations in other countries.
Authors: Tobias Hermle; Ronen Schneider; David Schapiro; Daniela A Braun; Amelie T van der Ven; Jillian K Warejko; Ankana Daga; Eugen Widmeier; Makiko Nakayama; Tilman Jobst-Schwan; Amar J Majmundar; Shazia Ashraf; Jia Rao; Laura S Finn; Velibor Tasic; Joel D Hernandez; Arvind Bagga; Sawsan M Jalalah; Sherif El Desoky; Jameela A Kari; Kristen M Laricchia; Monkol Lek; Heidi L Rehm; Daniel G MacArthur; Shrikant Mane; Richard P Lifton; Shirlee Shril; Friedhelm Hildebrandt Journal: J Am Soc Nephrol Date: 2018-06-29 Impact factor: 10.121
Authors: Ginevra Zanni; P De Magistris; M Nardella; E Bellacchio; S Barresi; A Sferra; A Ciolfi; M Motta; H Lue; D Moreno-Andres; M Tartaglia; E Bertini; Wolfram Antonin Journal: Cerebellum Date: 2019-06 Impact factor: 3.847
Authors: Daniela A Braun; Svjetlana Lovric; David Schapiro; Ronen Schneider; Jonathan Marquez; Maria Asif; Muhammad Sajid Hussain; Ankana Daga; Eugen Widmeier; Jia Rao; Shazia Ashraf; Weizhen Tan; C Patrick Lusk; Amy Kolb; Tilman Jobst-Schwan; Johanna Magdalena Schmidt; Charlotte A Hoogstraten; Kaitlyn Eddy; Thomas M Kitzler; Shirlee Shril; Abubakar Moawia; Kathrin Schrage; Arwa Ishaq A Khayyat; Jennifer A Lawson; Heon Yung Gee; Jillian K Warejko; Tobias Hermle; Amar J Majmundar; Hannah Hugo; Birgit Budde; Susanne Motameny; Janine Altmüller; Angelika Anna Noegel; Hanan M Fathy; Daniel P Gale; Syeda Seema Waseem; Ayaz Khan; Larissa Kerecuk; Seema Hashmi; Nilufar Mohebbi; Robert Ettenger; Erkin Serdaroğlu; Khalid A Alhasan; Mais Hashem; Sara Goncalves; Gema Ariceta; Mercedes Ubetagoyena; Wolfram Antonin; Shahid Mahmood Baig; Fowzan S Alkuraya; Qian Shen; Hong Xu; Corinne Antignac; Richard P Lifton; Shrikant Mane; Peter Nürnberg; Mustafa K Khokha; Friedhelm Hildebrandt Journal: J Clin Invest Date: 2018-09-04 Impact factor: 14.808