Nineteen novel NPHS1 mutations in a worldwide cohort of patients with congenital nephrotic syndrome (CNS)
| Autor: | Shazia Ashraf, Verena Matejas, Detlef Bockenhauer, Susanne Held, Saskia F. Heeringa, Thomas J. Neuhaus, Martin Zenker, Khemchand N. Moorani, Virginia Vega-Warner, Gil Chernin, James W. MacDonald, Pawaree Saisawat, Jameela A. Kari, Friedhelm Hildebrandt, Christopher N. Vlangos, Bugsu Ovunc, Dominik S. Schoeb |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Heterozygote Nephrotic Syndrome Genotype Nonsense mutation Global Health medicine.disease_cause Compound heterozygosity Cohort Studies Humans Medicine Missense mutation Family Congenital nephrotic syndrome Genetics Transplantation Mutation business.industry Homozygote Infant Newborn Infant Membrane Proteins Exons Prognosis medicine.disease Phenotype Nephrology Immunology Slit diaphragm Female Original Article business Nephrotic syndrome |
| Zdroj: | Nephrology Dialysis Transplantation. 25:2970-2976 |
| ISSN: | 1460-2385 0931-0509 |
| DOI: | 10.1093/ndt/gfq088 |
| Popis: | 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 90days 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 90days, while the other one did not manifest until the age of 2years. Both siblings also unexpectedly experienced an episode of partial remission upon steroid treatment. |
| Databáze: | OpenAIRE |
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