Focal segmental glomerulosclerosis-6 is an autosomal recessive childhood-onset kidney disorder manifest clinically by the nephrotic syndrome, which is characterized by proteinuria, hematuria, hypoalbuminemia, and progressive renal failure. It is a disease of the glomerular podocyte (summary by Mele ... Focal segmental glomerulosclerosis-6 is an autosomal recessive childhood-onset kidney disorder manifest clinically by the nephrotic syndrome, which is characterized by proteinuria, hematuria, hypoalbuminemia, and progressive renal failure. It is a disease of the glomerular podocyte (summary by Mele et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of focal segmental glomerulosclerosis and nephrotic syndrome, see FSGS1 (603278).
Mele et al. (2011) reported an 18-year-old Italian girl, born of consanguineous parents, who presented at age 9 years with nephrotic-range proteinuria, microhematuria, hypoalbuminemia, and edema. Renal biopsy showed 30% of glomeruli with segmental sclerohyalinosis with capsular crescents ... Mele et al. (2011) reported an 18-year-old Italian girl, born of consanguineous parents, who presented at age 9 years with nephrotic-range proteinuria, microhematuria, hypoalbuminemia, and edema. Renal biopsy showed 30% of glomeruli with segmental sclerohyalinosis with capsular crescents and 30% of glomeruli with collapse. There was also focal mesangial hyperplasia and tubular atrophy with tubulitis and interstitial inflammatory infiltrates. There were diffuse glomerular and peritubular deposits of Ig antibodies and complement components. Despite therapy with steroids and cyclosporine, she developed end-stage renal disease at age 13 years and underwent successful kidney transplant at age 17. Two younger sibs were similarly affected, but they showed a partial response to glucocorticoid and cyclosporine therapy. Mele et al. (2011) also reported a Turkish girl from a consanguineous kindred who presented at age 1 year with edema, proteinuria, hematuria, and hypoalbuminemia. Renal biopsy at age 4 years showed segmental or global sclerosis of 20% glomeruli and focal tubular dilatation and atrophy with interstitial fibrosis. Electron microscopy showed effacement of the foot processes, microvillus transformation of podocytes, focal thickening and disorganization of the glomerular basement membrane, and focal expansion of the mesangial matrix. She achieved partial remission with medical treatment. An older sister had died at age 6 years of progressive renal failure.
By genomewide linkage analysis followed by high-throughput sequencing of a consanguineous Italian family with FSGS6, Mele et al. (2011) identified a homozygous mutation in the MYO1E gene (A159P; 601479.0001) on chromosome 15q21. Sequencing of the MYO1E gene in ... By genomewide linkage analysis followed by high-throughput sequencing of a consanguineous Italian family with FSGS6, Mele et al. (2011) identified a homozygous mutation in the MYO1E gene (A159P; 601479.0001) on chromosome 15q21. Sequencing of the MYO1E gene in 52 additional patients with FSGS or mesangial sclerosis identified a homozygous truncating mutation (Y695X; 601479.0002) in a Turkish girl with FSGS. The MYO1E protein localizes to the plasma membrane of the podocyte and plays a role in normal glomerular filtration. Cellular studies showed that the A159P-mutant protein mislocalized to the cytoplasm, did not colocalize with F-action, and was unable to promote podocyte migration, indicating a defect in normal MYO1E function.