title: NPHS1 gene mutations confirm congenital nephrotic syndrome in four Brazilian cases: A novel mutation is described.
abstract: OBJECTIVE
  Autosomal recessive mutations in NPHS1 gene are a common cause of congenital nephrotic syndrome (CNS). The disorder is characterized by massive proteinuria that manifests in utero or in the neonatal period during the first 3 months of life. NPHS1 encodes nephrin, a member of the immunoglobulin family of cell adhesion molecules and the main protein expressed at the renal slit diaphragm. Currently, there are approximately 250 mutations described in the NPHS1 gene distributed among all nephrin domains. The main objective of this study was to perform the analysis of the NPHS1 gene in patients with congenital nephrotic syndrome in order to determine the molecular cause of the disease.
  
  
  METHODS
  Direct sequencing of NPHS1 gene in four children was performed.
  
  
  RESULTS
  Each patient was heterozygous for two pathogenic mutations disclosing the molecular cause of the disease in 100% of the cases. We identified six different mutations, consisting of one in-frame deletion, one frameshift, and four missense substitutions. The p.Val736Met mutation that is described here for the first time was considered pathogenic by different mutation predictive algorithms. Regardless of the type of mutation, three patients had a bad outcome and died
  
  
  CONCLUSIONS
  Despite the small size of the cohort, this study contributed to the increasing number of deleterious mutations in the NPHS1 gene by describing a new mutation. Also, since we identified NPHS1 pathogenic mutations as the cause of the disease in all cases analyzed, it might be a frequent cause of CNS in the South Eastern region of Brazil, although the analysis of a larger sample is required to obtain more indicative epidemiological data.
authors.affiliation: Center for Molecular Biology and Genetic Engineering, University of Campinas, Sao Paulo, Brazil.
authors.forename: Mara S
authors.initials: MS
authors.lastname: Guaragna
authors.affiliation: Nephrology Center of University Hospital Pedro Ernesto, Rio de Janeiro, Brazil.
authors.forename: Thaís Lira
authors.initials: TL
authors.lastname: Cleto
authors.affiliation: Center for Molecular Biology and Genetic Engineering, University of Campinas, Sao Paulo, Brazil.
authors.forename: Marcela Lopes
authors.initials: ML
authors.lastname: Souza
authors.affiliation: Pediatric Nephrology, Department of Pediatrics, School of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil.
authors.forename: Anna Cristina G B
authors.initials: AC
authors.lastname: Lutaif
authors.affiliation: Pediatric Endocrinology, Faculty of Medicine, University of Brasilia, Brasilia, Federal District, Brazil.
authors.forename: Luiz Cláudio Gonçalves
authors.initials: LC
authors.lastname: de Castro
authors.affiliation: Pediatric Department, Faculty of Medicine, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Maria Goretti Moreira Guimarães
authors.initials: MG
authors.lastname: Penido
authors.affiliation: Department of Medical Genetics, School of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil.
authors.forename: Andréa T
authors.initials: AT
authors.lastname: Maciel-Guerra
authors.affiliation: Pediatric Nephrology, Department of Pediatrics, School of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil.
authors.forename: Vera M S
authors.initials: VM
authors.lastname: Belangero
authors.affiliation: Interdisciplinary study group of determination and sex differentiation, School of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil.|Pediatric Research Center, School of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil.|Pediatric Endocrinology, Pediatric Department, School of Medical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil.
authors.forename: Gil
authors.initials: G
authors.lastname: Guerra-Junior
authors.affiliation: Center for Molecular Biology and Genetic Engineering, University of Campinas, Sao Paulo, Brazil.
authors.forename: Maricilda P
authors.initials: MP
authors.lastname: De Mello
mesh_terms: D001938:Brazil; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D017809:Fatal Outcome; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D009392:Nephrectomy; D009404:Nephrotic Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D010641:Phenotype; D016896:Treatment Outcome
chemical_list: D005819:Genetic Markers; D008565:Membrane Proteins; C113267:nephrin
keywords: NPHS1 gene; congenital nephrotic syndrome; nephrin; novel mutation