Characterization of a large Lebanese family segregating IgA nephropathy.

BACKGROUND: Familial aggregation of IgA nephropathy (IgAN) suggests that genetic factors contribute to the development of this trait. Because clinical manifestations in IgAN families are often limited to episodic haematuria, large kindreds tractable to linkage analysis have been difficult to identify. METHODS: We identified a large Lebanese-Druze kindred ascertained via an index case with biopsy-documented IgAN. We performed systematic screening of 38 family members and tested linkage to reported IgAN loci. RESULTS: Screening of this family identified 16 affected individuals, including 2 individuals with biopsy-documented IgAN and 14 with chronic renal failure or abnormal urinalyses on at least three separate occasions. This kindred spanned five generations and contained five consanguineous unions. Multigenerational inheritance suggested that autosomal dominant inheritance was most likely. Phenotypic manifestations among affected individuals varied from isolated haematuria to advanced renal failure necessitating transplantation; one instance of IgAN recurrence after transplantation was also documented. Older age was associated with greater severity of disease and higher incidence of renal failure. Parametric and non-parametric analyses with 33 microsatellite markers did not reveal any evidence of linkage to reported IgAN loci on chromosomes 6q22-23, 2q36 and 4q22-31. CONCLUSIONS: We describe one of the largest multigenerational IgAN kindreds reported to date. The high incidence of renal failure among older generations suggests a significant risk of progression to renal failure. We found no evidence of linkage to known loci, suggesting that familial IgAN encompasses multiple subtypes that will require distinction based on genetic or biomarker data.