title: Clinical, histopathologic, and genetic studies in nine families with focal segmental glomerulosclerosis.
abstract: BACKGROUND
  Familial forms of focal segmental glomerulosclerosis (FSGS) are caused by mutations in genes at 1q25-31 (gene for steroid-resistant nephrotic syndrome 2 [NPHS2]), 11q21-22, 19q13 (gene for alpha-actinin 4 and NPHS1), and at additional unidentified chromosomal loci.
  
  
  METHODS
  We describe clinical and histopathologic features and results of linkage analysis in nine consecutive index cases with familial FSGS who, together with their families, were referred for genetic studies.
  
  
  RESULTS
  Two of the index cases presented in childhood (22%) and seven cases presented in adolescence or adulthood (78%). Six of their families (67%), including the two cases with childhood-onset disease, showed probable autosomal recessive inheritance. FSGS segregated at the 1q25-31 locus in two of these families and at the 11q21-22 locus in four families. None had disease caused by mutations in genes at the 19q13 locus, and no locus was identified in the three remaining families. Clinical features of proteinuria, minimal hematuria, hypertension, preeclampsia, and progressive renal impairment were usually present with autosomal recessive or dominant inheritance and with disease that segregated at the different loci. Eighteen renal biopsies from affected members of eight families showed a strong correlation between tubulointerstitial damage and percentage of obsolescent glomeruli (rho = +0.76; P < 0.01). None of the 13 patients from eight families who underwent transplantation developed recurrent FSGS in their grafts. In general, carriers of autosomal recessive disease had no distinctive clinical features apart from the development of preeclampsia in successive pregnancies.
  
  
  CONCLUSIONS
  Familial forms of FSGS are not uncommon, and presentation frequently is in adolescence or adulthood, even when inheritance is autosomal recessive. Furthermore, carriers of autosomal recessive FSGS often have no distinctive phenotype.
authors.affiliation: University Department of Medicine, Austin and Repatriation Medical Centre, Heidelberg, VIC, Australia.
authors.forename: Kesha
authors.initials: K
authors.lastname: Rana
authors.forename: Nicole
authors.initials: N
authors.lastname: Isbel
authors.forename: Mark
authors.initials: M
authors.lastname: Buzza
authors.forename: Hayat
authors.initials: H
authors.lastname: Dagher
authors.forename: Paul
authors.initials: P
authors.lastname: Henning
authors.forename: Gad
authors.initials: G
authors.lastname: Kainer
authors.forename: Judy
authors.initials: J
authors.lastname: Savige
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D001706:Biopsy; D002648:Child; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D005808:Genes, Recessive; D018740:Genetic Heterogeneity; D005923:Glomerulosclerosis, Focal Segmental / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D006417:Hematuria / Q000209:etiology; D006801:Humans; D006977:Hypertension, Renal / Q000209:etiology; D007668:Kidney / Q000473:pathology; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011225:Pre-Eclampsia / Q000209:etiology; D011247:Pregnancy; D011507:Proteinuria / Q000209:etiology