Molecular analysis of uromodulin and SAH genes, positional candidates for autosomal dominant medullary cystic kidney disease linked to 16p12

Background. The location of a second genetic locus for autosomal dominant m edullary cystic kidney disease (ADMCKD) at chromosome 16p12 led us to furth er investigate the molecular analysis of the critical region where two gene s coding for uromodulin and SA proteins with renal specific functions, UMOD and SAH, are localized. Methods: We characterized the intron-exon boundary sequences by screening p hage and BAC DNA genomic clones for the development of new molecular tools functional to the mutation analysis of UMOD and SAH genes. Results: No consistent mutations for ADMCKD2 were found in the UMOD and SAH genes. We identified a silent polymorphism in the UMOD gene at codon C174 which co-segregates with the disease in the ADMCKD2 family. Conclusions: This study excludes the involvement of uromodulin and SAH gene s in ADMCKD2, and provides new tools for their molecular analysis in other diseases.