BACKGROUND: Mutations in the NPHS1 and NPHS2 genes are among the main causes of early-onset and familial steroid resistant nephrotic syndrome respectively. This study was carried out to assess the frequencies of mutations in these two genes in a cohort of Pakistani pediatric NS patients. METHODS: Mutation analysis was carried out by direct sequencing of the NPHS1 and NPHS2 genes in 145 nephrotic syndrome (NS) patients. This cohort included 36 samples of congenital or infantile onset NS cases and 39 samples of familial cases obtained from 30 families. RESULTS: A total of 7 homozygous (6 novel) mutations were found in the NPHS1 gene and 4 homozygous mutations in the NPHS2 gene. All mutations in the NPHS1 gene were found in the early onset cases. Of these, one patient has a family history of NS. Homozygous p.R229Q mutation in the NPHS2 gene was found in two children with childhood-onset NS. CONCLUSIONS: Our results show a low prevalence of disease causing mutations in the NPHS1 (22% early onset, 5.5% overall) and NPHS2 (3.3% early onset and 3.4% overall) genes in the Pakistani NS children as compared to the European populations. In contrast to the high frequency of the NPHS2 gene mutations reported for familial SRNS in Europe, no mutation was found in the familial Pakistani cases. To our knowledge, this is the first comprehensive screening of the NPHS1 and NPHS2 gene mutations in sporadic and familial NS cases from South Asia.
BACKGROUND: Mutations in the NPHS1 and NPHS2 genes are among the main causes of early-onset and familial steroid resistant nephrotic syndrome respectively. This study was carried out to assess the frequencies of mutations in these two genes in a cohort of Pakistani pediatric NSpatients. METHODS: Mutation analysis was carried out by direct sequencing of the NPHS1 and NPHS2 genes in 145 nephrotic syndrome (NS) patients. This cohort included 36 samples of congenital or infantile onset NS cases and 39 samples of familial cases obtained from 30 families. RESULTS: A total of 7 homozygous (6 novel) mutations were found in the NPHS1 gene and 4 homozygous mutations in the NPHS2 gene. All mutations in the NPHS1 gene were found in the early onset cases. Of these, one patient has a family history of NS. Homozygous p.R229Q mutation in the NPHS2 gene was found in two children with childhood-onset NS. CONCLUSIONS: Our results show a low prevalence of disease causing mutations in the NPHS1 (22% early onset, 5.5% overall) and NPHS2 (3.3% early onset and 3.4% overall) genes in the Pakistani NSchildren as compared to the European populations. In contrast to the high frequency of the NPHS2 gene mutations reported for familial SRNS in Europe, no mutation was found in the familial Pakistani cases. To our knowledge, this is the first comprehensive screening of the NPHS1 and NPHS2 gene mutations in sporadic and familial NS cases from South Asia.
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: Markus M Rinschen; Xiongwu Wu; Tim König; Trairak Pisitkun; Henning Hagmann; Caroline Pahmeyer; Tobias Lamkemeyer; Priyanka Kohli; Nicole Schnell; Bernhard Schermer; Stuart Dryer; Bernard R Brooks; Pedro Beltrao; Marcus Krueger; Paul T Brinkkoetter; Thomas Benzing Journal: J Am Soc Nephrol Date: 2014-02-07 Impact factor: 10.121
Authors: Shanika Nanayakkara; S T M L D Senevirathna; Nipuna B Parahitiyawa; Tilak Abeysekera; Rohana Chandrajith; Neelakanthi Ratnatunga; Toshiaki Hitomi; Hatasu Kobayashi; Kouji H Harada; Akio Koizumi Journal: Environ Health Prev Med Date: 2015-06-25 Impact factor: 3.674
Authors: Stefanie Weber; Anja K Büscher; Henning Hagmann; Max C Liebau; Christian Heberle; Michael Ludwig; Sabine Rath; Martin Alberer; Antje Beissert; Martin Zenker; Peter F Hoyer; Martin Konrad; Hanns-Georg Klein; Julia Hoefele Journal: Pediatr Nephrol Date: 2015-08-07 Impact factor: 3.714