Journal Article

Nineteen novel <i>NPHS1</i> mutations in a worldwide cohort of patients with congenital nephrotic syndrome (CNS)

Dominik S. Schoeb, Gil Chernin, Saskia F. Heeringa, Verena Matejas, Susanne Held, Virginia Vega-Warner, Detlef Bockenhauer, Christopher N. Vlangos, Khemchand N. Moorani, Thomas J. Neuhaus, Jameela A. Kari, James MacDonald, Pawaree Saisawat, Shazia Ashraf, Bugsu Ovunc, Martin Zenker and Friedhelm Hildebrandt

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 25, issue 9, pages 2970-2976
Published in print September 2010 | ISSN: 0931-0509
Published online February 2010 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfq088
Nineteen novel NPHS1 mutations in a worldwide cohort of patients with congenital nephrotic syndrome (CNS)

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Background. Recessive mutations in the NPHS1 gene encoding nephrin account for ∼40% of infants with congenital nephrotic syndrome (CNS). CNS is defined as steroid-resistant nephrotic syndrome (SRNS) within the first 90 days of life. Currently, more than 119 different mutations of NPHS1 have been published affecting most exons.

Methods. We here performed mutational analysis of NPHS1 in a worldwide cohort of 67 children from 62 different families with CNS.

Results. We found bi-allelic mutations in 36 of the 62 families (58%) confirming in a worldwide cohort that about one-half of CNS is caused by NPHS1 mutations. In 26 families, mutations were homozygous, and in 10, they were compound heterozygous. In an additional nine patients from eight families, only one heterozygous mutation was detected. We detected 37 different mutations. Nineteen of the 37 were novel mutations (∼51.4%), including 11 missense mutations, 4 splice-site mutations, 3 nonsense mutations and 1 small deletion. In an additional patient with later manifestation, we discovered two further novel mutations, including the first one affecting a glycosylation site of nephrin.

Conclusions. Our data hereby expand the spectrum of known mutations by 17.6%. Surprisingly, out of the two siblings with the homozygous novel mutation L587R in NPHS1, only one developed nephrotic syndrome before the age of 90 days, while the other one did not manifest until the age of 2 years. Both siblings also unexpectedly experienced an episode of partial remission upon steroid treatment.

Keywords: mutation analysis; nephrotic syndrome; NPHS1

Journal Article.  4181 words.  Illustrated.

Subjects: Nephrology

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