Exclusion of the candidate genes ACE and Bcl-2 for six families with nephronophthisis not linked to the NPH1 locus

Background. Nephronophthisis (NPH) is an autosomal recessively transmitted kidney disease, characterized by cyst formation at the cortico-medullary ju nction, and a sclerosing tubulointerstitial nephropathy. Juvenile nephronop hthisis (NPH1) is the most common genetic cause of renal failure in childre n and maps to chromosome 2q12-q13. The responsible gene NPHP1 has been iden tified and encodes for nephrocystin. Not all families with NPH demonstrate linkage to that locus. Methods. We studied six families with NPH without linkage to the NPH1 locus . In order to attempt identification of a new causative gene, the candidate genes ACE (angiotensin converting enzyme) and Bcl-2 (B cell leukaemia/lymp homa 2 gene) originating from mouse models, were examined. For the six fami lies highly polymorphic microsatellites covering the whole candidate gene r egions were haplotyped and linkage analysis was performed. Results. Haplotype analyses of all families examined were incompatible with linkage of the disease status to A CE or Bcl-2. Linkage analysis excluded both candidate gene regions with a LOD-score of < -2. Conclusions. This study excluded the candidate genes ACE and Bcl-2 for NPH. Additional linkage studies need to be performed in order to identify furth er genes responsible for nephronophthisis.