Novel mutations in steroid-resistant nephrotic syndrome diagnosed in Tunisian children
| Autor: | Ibtihel M'barek, Marie Claire Gubler, Abdelaziz Harbi, Asma Omezzine, Audrey Pawtowski, Saoussen Abroug, Corinne Antignac, Ali Bouslama |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Nephrotic Syndrome Tunisia Adolescent Genotype DNA Mutational Analysis Disease Biology Exon Young Adult medicine Humans Child WT1 Proteins Gene Exome sequencing Genetics PLCE1 Haplotype Infant Newborn Intracellular Signaling Peptides and Proteins Infant Membrane Proteins Exons medicine.disease Steroid-resistant nephrotic syndrome Pedigree Nephrology Child Preschool Pediatrics Perinatology and Child Health Mutation Female Laminin Nephrotic syndrome |
| Zdroj: | Pediatric nephrology (Berlin, Germany). 26(2) |
| ISSN: | 1432-198X |
| Popis: | Steroid-resistant nephrotic syndrome (NS) remains one of the most intractable causes of end-stage renal disease in the first two decades of life. Several genes have been involved including NPHS1, NPHS2, WT1, PLCE1, and LAMB2. Our aim was to identify causative mutations in these genes, in 24 children belonging to 13 families with NS manifesting with various ages of onset. We performed haplotype analysis and direct exon sequencing of NPHS1, NPHS2, PLCE1, LAMB2, and the relevant exons 8 and 9 of WT1. Ten different pathogenic mutations were detected in seven families concerning four genes (NPHS1 (3/7), LAMB2 (2/7), NPHS2 (1/7), and WT1 (1/7)). Five of the detected mutations were novel; IVS9 + 2 T > C and p.D616G in NPHS1; p.E371fsX16 in NPHS2, and p.E705X and p.D1151fsX23 in LAMB2. Nine of 24 patients failed to be categorized by mutational analysis. Our study extends the spectrum of abnormalities underlying NS, by reporting novel mutations in the NPHS1 and NPHS2 genes and the first cases of LAMB2 mutations in Tunisia. Congenital and infantile NS can be explained by mutations in NPHS1, NPHS2, WT1, or LAMB2 genes. The identification of additional genes mutated in NS can be anticipated. |
| Databáze: | OpenAIRE |
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