Focal segmental glomerulosclerosis (FSGS) is a pathologic entity associated clinically with proteinuria, the nephrotic syndrome (NPHS), and progressive loss of renal function. It is a common cause of end-stage renal disease (ESRD) (Meyrier, 2005).
Dominant intermediate ... Focal segmental glomerulosclerosis (FSGS) is a pathologic entity associated clinically with proteinuria, the nephrotic syndrome (NPHS), and progressive loss of renal function. It is a common cause of end-stage renal disease (ESRD) (Meyrier, 2005). Dominant intermediate Charcot-Marie-Tooth disease E and focal segmental glomerulonephritis (CMTDIE; 614455) is also caused by heterozygous mutation in the INF2 gene. For a general phenotypic description and a discussion of genetic heterogeneity of focal segmental glomerulosclerosis and nephrotic syndrome, see FSGS1 (603278).
Brown et al. (2010) studied 11 families with focal segmental glomerulosclerosis in which affected individuals displayed shared features, including onset of disease in adolescence or adulthood and proteinuria that was typically moderate. Microscopic hematuria and hypertension were seen ... Brown et al. (2010) studied 11 families with focal segmental glomerulosclerosis in which affected individuals displayed shared features, including onset of disease in adolescence or adulthood and proteinuria that was typically moderate. Microscopic hematuria and hypertension were seen in some individuals, and many had proteinuria in the nephrotic range, but none had other manifestations of the clinical nephrotic syndrome (see 256300) such as hypoalbuminemia or edema. The disease and the proteinuria were progressive, often leading to end-stage renal disease. Renal biopsies showed the presence of FSGS on light microscopy, and electron microscopy showed focal areas of podocyte foot-process effacement, typical of secondary and some genetic forms of FSGS, as well as areas where foot processes and slit-diaphragms were well preserved. Brown et al. (2010) also observed unusually prominent actin bundles within the foot processes. Noting that glomerular hypertrophy was not a prominent feature of the biopsies, and that there were no perihilar collapsing or cellular lesions, they stated that these biopsies would be characterized as 'FSGS, not otherwise specified' in the classification scheme of D'Agati et al. (2004).
In 2 large families segregating autosomal dominant FSGS mapping to chromosome 14q32, Brown et al. (2010) sequenced 15 candidate genes and identified heterozygous missense mutations in the INF2 gene (610982) that segregated with disease (610982.0001 and 610982.0002) in ... In 2 large families segregating autosomal dominant FSGS mapping to chromosome 14q32, Brown et al. (2010) sequenced 15 candidate genes and identified heterozygous missense mutations in the INF2 gene (610982) that segregated with disease (610982.0001 and 610982.0002) in both families. Sequencing of the INF2 gene in 91 unrelated individuals with familial FSGS identified 9 additional families with heterozygous mutations in the INF2 gene (see, e.g., 610982.0003-610982.0005).