title: Report of novel genetic variation in NPHS2 gene associated with idiopathic nephrotic syndrome in South Indian children.
abstract: BACKGROUND
  Steroid-resistant nephrotic syndrome (SRNS) is found in 10-20 % of children with idiopathic nephrotic syndrome (INS). In SRNS patients, common histopathological subtypes are Focal segmental glomerulosclerosis (FSGS) (53 %) and minimal change disease (MCD) (27 %). Familial forms of FSGS constitute podocyte diseases with varying severity and age of onset. Podocin gene (NPHS2) mutations cause childhood-onset steroid-resistant FSGS and MCD to adult-onset FSGS. In view of genetic variations and susceptibility to the disease, the present investigation was undertaken to study the pattern of genetic mutation in children from South India.
  
  
  METHODS
  Mutation analysis was carried out by direct sequencing of the entire NPHS2 gene (eight exons) using specific primers in 200 INS (100 SRNS and 100 steroid sensitive) children and 100 healthy controls. The allele and genotype frequencies of NPHS2 gene were calculated for both cases and controls as per Hardy-Weinberg equilibrium.
  
  
  RESULTS
  Among the SRNS patients, 18 % revealed both heterozygous and homozygous mutations. Out of 12 mutations, 8 were homozygous and 4 were heterozygous. Interestingly, we found two novel SNPs in exon 4 of NPHS2 gene, which are documented and submitted to dbsnp database (Ref rs12401711 and rs12401708).
  
  
  CONCLUSIONS
  Mutational analysis of NPHS2 would be advisable at the start of treatment. The genetic variations detected in the study would serve as the important molecular marker in treating the children's at early stage, which also enables to detect carriers, prenatal diagnosis and provide genetic counseling to couples at risk.
authors.affiliation: V Clin Bio Labs, Central Research Facility, Sri Ramachandra University, Porur, Chennai, 600 116, India.
authors.forename: Mohanapriya Chinambedu
authors.initials: MC
authors.lastname: Dhandapani
authors.affiliation: Department of Human Genetics, Sri Ramachandra University, Porur, Chennai, 600 116, India.
authors.forename: Vettriselvi
authors.initials: V
authors.lastname: Venkatesan
authors.affiliation: Department of Pediatric Nephrology, Mehta Children's Hospital, Chennai, 600 031, India.
authors.forename: Nammalwar Bollam
authors.initials: NB
authors.lastname: Rengaswamy
authors.affiliation: Department of Medical Genetics, Kanchi Kamakoti CHILDS Trust Hospital, Chennai, 600 034, India.
authors.forename: Kalpana
authors.initials: K
authors.lastname: Gowrishankar
authors.affiliation: Department of Pediatric Nephrology, Mehta Children's Hospital, Chennai, 600 031, India.
authors.forename: Sudha
authors.initials: S
authors.lastname: Ekambaram
authors.affiliation: Department of Nephrology, Sri Ramachandra University, Porur, Chennai, 600 116, India.
authors.forename: Prabha
authors.initials: P
authors.lastname: Sengutavan
authors.affiliation: Department of Human Genetics, Sri Ramachandra University, Porur, Chennai, 600 116, India. venkip@yahoo.com.
authors.forename: Venkatachalam
authors.initials: V
authors.lastname: Perumal
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing / Q000379:methods; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007194:India; D007223:Infant; 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; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein
keywords: NPHS2 mutations; Polymorphism; Steroid-resistant nephrotic syndrome
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