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

Background. Familial nephrotic syndrome (NS) has both autosomal dominant an d recessive forms of inheritance. Recent studies in families with an autoso mal dominant form of focal segmental glomerulosclerosis (FSGS) have been at odds concerning linkage to chromosome 19q13 (Mathis et al, Kidney Int 53:2 82-286, 1998; Winn et al, Kidney mr 55:1241-1246, 1999); suggesting genetic heterogeneity. This study examines the clinical features and confirms link age to chromosome 19q13 in a family with autosomal dominant NS. Methods. DNA samples were obtained from 16 of 17 family members. Genomic DN A was isolated, and polymerase chain reaction was performed for five marker s spanning the area of interest on chromosome 19q13. Data were evaluated us ing two-and six-point linkage analysis. Results. Clinical features included presentation of NS in childhood, steroi d unresponsiveness, and slow progression to renal failure. Renal biopsy in affected family members showed lesions ranging from minimal change to mesan gial proliferative glomerulonephritis to FSGS. Linkage was confirmed betwee n 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 1 9q13, defined by markers D19S425 and D19S220. Conclusions. This study confirms the Mathis et al report of linkage to chro mosome 19q13 in a family with autosomal dominant NS. However, there were no table differences in the presenting clinical and histopathologic features o f our affected family members compared with those of Mathis et al. This sug gests that the gene on chromosome 19q13 may be responsible for considerable phenotypic heterogeneity and variable expression in both clinical presenta tion and renal histopathology.