Podocyte-associated gene mutation screening in a heterogeneous cohort of patients with sporadic focal segmental glomerulosclerosis

Nephrol Dial Transplant. 2014 Nov;29(11):2062-9. doi: 10.1093/ndt/gft532. Epub 2014 Feb 4.


Background: The utility of genetic testing in sporadic focal segmental glomerulosclerosis (FSGS) is unclear. We sought to determine the frequency of podocyte-related gene mutations in a heterogeneous population of adults and children with biopsy-proven FSGS.

Methods: The prevalence of pathogenic mutations in five genes (NPHS2, TRPC6, ACTN4, INF2 and PLCE1) and of APOL1 risk alleles (G1 and G2) was ascertained in children and adults diagnosed between 1984 and 2011 with FSGS by renal biopsy. Clinical data were extracted from medical records.

Results: A total of 65 patients (28 children, 37 adults) with sporadic FSGS were identified (34 females, 31 males), with a mean age of 25 ± 16 years (range from 3 to 62 years). The majority of patients were African American (39 African American, 21 White and 2 Hispanic). We identified biallelic pathogenic NPHS2 mutations in 2 of 28 (7.1%) children, both of whom were of non-Hispanic Caucasian background. A homozygous NPHS2 p.R138Q/p.R138Q mutation was detected in a 5-year-old Caucasian female. Two compound heterozygous NPHS2 mutations p.R138Q/p.R229Q were identified in a 7-year-old Caucasian male patient. One novel, potentially pathogenic non-synonymous variant in INF2 was identified in an African American patient. The proportion of African Americans with two APOL1 risk alleles was 69.2%.

Conclusions: This study delineates a role for genetic testing for NPHS2 in children with biopsy-proven sporadic FSGS. Further studies which specify clinical and pathological details of patients will help further define whether there are specific populations that warrant systematic testing of other podocyte-related genes in sporadic FSGS.

Keywords: APOL1; genetic screening; podocyte-related gene mutations; sporadic FSGS; steroid-resistant nephrotic syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biopsy
  • Child
  • Child, Preschool
  • DNA / genetics*
  • DNA Mutational Analysis
  • Female
  • Genetic Testing
  • Glomerulosclerosis, Focal Segmental / genetics*
  • Glomerulosclerosis, Focal Segmental / metabolism
  • Glomerulosclerosis, Focal Segmental / pathology
  • Heterozygote
  • Homozygote
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Middle Aged
  • Mutation*
  • Podocytes / metabolism
  • Podocytes / pathology*
  • Retrospective Studies
  • Young Adult


  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • DNA