title: Genetic mutation in Egyptian children with steroid-resistant nephrotic syndrome.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Human Genetics and Genome Research Division, Clinical Genetics Department, National Research Centre, Cairo, Egypt. Electronic address: nula_m@hotmail.com.
authors.forename: Manal Micheal
authors.initials: MM
authors.lastname: Thomas
authors.affiliation: Medical Molecular Genetics Department and Genome Research Division, National Research Centre, Cairo, Egypt.
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Abdel-Hamid
authors.affiliation: Child Health Department, National Research Centre, Cairo, Egypt.
authors.forename: Nermine Nabil
authors.initials: NN
authors.lastname: Mahfouz
authors.affiliation: Kasr Al Ainy School of Medicine, Cairo University, Cairo, Egypt.
authors.forename: Emad Emil
authors.initials: EE
authors.lastname: Ghobrial
mesh_terms: 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 / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D009404:Nephrotic Syndrome / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics
chemical_list: D005819:Genetic Markers; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein
keywords: Egyptian children; NPHS2; steroid-resistant nephrotic syndrome