Familial nephrotic syndrome: clinical spectrum and linkage to chromosome 19q13

Kidney Int. 2000 Mar;57(3):875-81. doi: 10.1046/j.1523-1755.2000.057003875.x.


Background: Familial nephrotic syndrome (NS) has both autosomal dominant and recessive forms of inheritance. Recent studies in families with an autosomal dominant form of focal segmental glomerulosclerosis (FSGS) have been at odds concerning linkage to chromosome 19q13 (Mathis et al, Kidney Int 53:282-286, 1998; Winn et al, Kidney Int 55:1241-1246, 1999), suggesting genetic heterogeneity. This study examines the clinical features and confirms linkage to chromosome 19q13 in a family with autosomal dominant NS.

Methods: DNA samples were obtained from 16 of 17 family members. Genomic DNA was isolated, and polymerase chain reaction was performed for five markers spanning the area of interest on chromosome 19q13. Data were evaluated using two- and six-point linkage analysis.

Results: Clinical features included presentation of NS in childhood, steroid unresponsiveness, and slow progression to renal failure. Renal biopsy in affected family members showed lesions ranging from minimal change to mesangial proliferative glomerulonephritis to FSGS. Linkage was confirmed between the disease state and chromosome 19q13, with a maximum logarithm of odds (LOD) score of 2.41. Linkage was observed for a 7 cM region on chromosome 19q13, defined by markers D19S425 and D19S220.

Conclusions: This study confirms the Mathis et al report of linkage to chromosome 19q13 in a family with autosomal dominant NS. However, there were notable differences in the presenting clinical and histopathologic features of our affected family members compared with those of Mathis et al. This suggests that the gene on chromosome 19q13 may be responsible for considerable phenotypic heterogeneity and variable expression in both clinical presentation and renal histopathology.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Chromosomes, Human, Pair 19 / genetics*
  • Disease Progression
  • Female
  • Genetic Linkage / genetics*
  • Humans
  • Infant
  • Kidney Glomerulus / pathology
  • Lod Score
  • Male
  • Nephrotic Syndrome / genetics*
  • Nephrotic Syndrome / pathology
  • Nephrotic Syndrome / physiopathology*
  • Pedigree