Congenital nephrotic syndrome is a clinically and genetically heterogeneous disorder of the glomerular filtration barrier, characterized by massive proteinuria at or shortly after birth. Although nephrotic syndromes encompass a heterogeneous group of disorders, congenital nephrotic syndrome of the Finnish type (NPHS1 [MIM 256300]) is a distinct clinical entity. NPHS1 has an autosomal recessive mode of inheritance and is generally rare—except in Finland, where the incidence is∼ 1/10,000 live births (Norio 1966). Nephrin, a putative transmembrane protein belonging to the immunoglobulin family of cell-adhesion molecules, has been identified as the gene mutated in NPHS1, with loss-of-function deletion and missense mutations identified in Finnish and other white patients with NPHS1 (Kestilä et al. 1998; Lenkkeri et al. 1999). Several cases of NPHS1 have also been observed in other populations, with or without direct evidence of Finnish ancestry (Fuchshuber et al. 1996). On the basis of limited haplotype analysis, it has been argued that some cases of non-Finnish NPHS1 may have a common origin in Finland (Männikko et al. 1996).

We observed a high incidence of NPHS1 among the Old Order Mennonites in Lancaster County, Pennsylvania. In particular, we identified 26 cases of NPHS1, dating from the 1950s, in a very large inbred Mennonite kindred (population). Interestingly, all but one of the cases of NPHS1 in Mennonites occurred in a subgroup known as the “Groffdale Conference” Mennonites. The Groffdale Conference Mennonites formed as a result of a schism in the Weaverland Conference Mennonites of Lancaster County in 1927. The separation between the two groups was based on differing views regarding acculturation to American thought and society. The more conservative group formed the Groffdale Conference, whereas the more progressive members continued in the Weaverland Conference. At present, the populations and