1. ¹Division of Nephrology, Brescia University, Italy
2. ²Division of Nephrology, Columbia University, New York, New York, USA
3. ³Dialysis Unit, Ospedale di Desenzano, Brescia, Italy
4. ⁴Azienda Sanitaria Locale of Brescia, Italy
5. ⁵Pathology Department, Spedali Civili, Brescia, Italy
6. ⁶Departments of Genetics, Howard Hughes Medical Institute, Yale University, New Haven, Connecticut, USA

Correspondence: F Scolari, Divisione di Nefrologia, Spedali Civili di Brescia, P.le Spedali Civili, 1, Brescia 25125, Italy. E-mail: fscolar@tin.it

Received 15 September 2005; Revised 4 November 2005; Accepted 16 November 2005; Published online 22 February 2006.

Abstract

Hereditary factors are suspected to contribute to the pathogenesis of sporadic primary glomerulonephritis, but their contribution is difficult to delineate in the general population. We studied the prevalence of primary glomerulonephritis in an isolated population from the extreme northern Valtrompia valley, Northern Italy. Investigation of medical records, community urinary screening program and molecular characterization of the population's ancestry were performed; genealogies of affected individuals were researched. Forty-three patients with primary glomerulonephritis were identified: 25 had biopsy-proven disease (11 immunoglobulin A (IgA) nephropathy; eight mesangial proliferative glomerulonephritis without IgA deposits; four focal segmental glomerular sclerosis; two membranous nephropathy), and 18 had clinical glomerulonephritis. All 43 patients originated from three mountain villages (Collio, San Colombano, and Bovegno). In contrast, we found only four cases of primary glomerulonephritis in two nearby villages (Pezzaze and Tavernole) that shared similar population histories and lifestyles, demonstrating heterogeneity of risk factors for glomerulonephritis (P=3 10^-5). All 43 affected individuals could be traced back to common ancestors (XVI–XVII centuries), enabling the construction of three large pedigree including three parent–child affected pairs and five affected siblings pairs. Molecular data showed lower genetic diversity and increased inbreeding in the Valtrompia population compared to the control population. Molecular and genealogical evidence of limited set of founders and the absence of shared nephritogenic environmental factors suggest that our patients share a common genetic susceptibility to the development of primary glomerulonephritis. Further molecular study of our families will offer the possibility to shed light on the genetic background underlying these glomerular disorders.