Linkage of Type II and Type III cystinuria to 19q13.1: Codominant inheritance of two cystinuric alleles at 19q13.1 produces an extreme stone-forming phenotype

Cystinuria, a renal tubule disease affecting urinary cystine excretion with or without kidney stone formation, previously was mapped to chromosome reg ion 2p.21, Mutations in the gene SLC3A1 or NBAT, the reported candidate gen e for cystinuria at 2p.21, have been demonstrated in individuals with the a utosomal recessive Type I cystinuria phenotype. Recently, the Type III cyst inuria phenotype was mapped to chromosome region 19q13.1, Here we report a kindred of 39 persons in two families of cystinurics, Types II and III, tha t support linkage to 19q13.1 and exclude 2p.21, Based on a dominant model o f inheritance, two-point analysis of the entire pedigree produced a maximum lod score (Z(max)) of 3.82 at marker D19S425. Multipoint analysis yielded a lod score of 4.96 at this marker, and a resultant lod score of 5.90 using a codominant model of inheritance. Furthermore, a candidate gene interval of 8.9 cM, flanked by markers D19S225 and D19S223, was obtained using multi point and haplotype analyses. Thus, this kindred demonstrates the linkage o f Type II cystinuria to 19q13.1 and confirms the linkage of Type III cystin uria at 19q13.1 while excluding the marker D19S225 that was previously incl uded in the critical interval. (C) 1999 Wiley-Liss, Inc.