Genetic mutation in Egyptian children with steroid-resistant nephrotic syndrome.
BACKGROUND/PURPOSE
Nephrotic syndrome is the commonest etiology of proteinuria in children. Steroid-resistant nephrotic syndrome (SRNS) is defined by resistance to standard steroid therapy, and it continues to be one of the most intractable etiologies of renal failure. Molecular studies discovered specialized molecules in podocytes that play a role in proteinuria. Mutations in NPHS2 that encodes for podocin constitute a frequent cause of SRNS worldwide. This study aimed to screen for podocin mutations in SRNS Egyptian children and their parents.


METHODS
Our study included patients from 10 unrelated Egyptian families diagnosed with SRNS. Mutational analysis of the NPHS2 gene was performed by polymerase chain reaction amplification of the whole coding region of the gene and direct sequencing.


RESULTS
Positive consanguinity was detected in five cases, and four of them had a positive family history of SRNS in a family member. Mutational analysis of NPHS2 revealed pathogenic mutations in four cases (40%) including a novel missense in one patient (c.1A>T; p.M1L).


CONCLUSION
Our study concludes that mutations of NPHS2 gene are common among Egyptian children with SRNS. We support a model where ethnicity plays an important role in specific NPHS2 mutations, since a novel mutation was found in one patient in this study. Future study on a large number of Egyptian patients with SRNS is warranted to identify the actual genetic contribution of this gene in the development of SRNS in our population, which might help in patients' prognosis and management.
['Thomas|Manal Micheal|MM|', 'Abdel-Hamid|Mohamed S|MS|', 'Mahfouz|Nermine Nabil|NN|', 'Ghobrial|Emad Emil|EE|']
D000293:Adolescent D002648:Child D004252:DNA Mutational Analysis D004534:Egypt D005260:Female D005819:Genetic Markers D005820:Genetic Testing D006801:Humans D047908:Intracellular Signaling Peptides and Proteins D008297:Male D008565:Membrane Proteins D009154:Mutation D009404:Nephrotic Syndrome
Egyptian children steroid-resistant nephrotic syndrome NPHS2