Familial IgA nephropathy.

Abstract

To date, more than 90 families with multiple members with IgA nephropathy have been reported. The case for genetic predisposition as a cause of familial clustering of IgA nephropathy is supported by several factors, including variable time points in the onset of the disease in relatives with IgA nephropathy; the presence of abnormalities of IgA production in both affected and unaffected family members; the clustering of the birthplaces of ancestors of large pedigrees containing multiple affected members with IgA nephropathy, which suggests the existence of a "founder effect". Immunogenetic studies does not conclusively indicate that HLA is involved in the pathogenesis of IgA nephropathy. The specific mode of inheritance of familial IgA nephropathy is difficult to establish with certainty. IgA nephropathy may be a single gene trait with incomplete penetrance. Alternatively, a multifactorial genetic disease could account for the increased prevalence of the disorder among relatives of affected individuals. Clinicians must become aware that IgA nephropathy may aggregate within families in a substantial number of cases. The availability of multiplex families offers an ideal opportunity to design a molecular genetics approach to map the gene(s) or pathway(s) responsible for the development of IgA nephropathy.