Evidence of further genetic heterogeneity in autosomal dominant medullary cystic kidney disease

Background. Autosomal dominant medullary cystic kidney disease is a genetically heterogeneous nephropathy with clinical and morphological features similar to recessively inherited juvenile nephronophthisis. Recently, a second gene locus on chromosome 16p12, MCKD2 has been mapped [1] in addition to the known locus on chromosome 1q21 (MCKD1) [2]. In a previous study we have excluded linkage for three caucasian families to the MCKD1 locus [3]. Methods. Haplotype analysis was performed on 72 individuals (including 24 affected subjects), using a set of seven microsatellite markers spanning the critical region on chromosome 16p12-p13 of about 10.5 cM. Results. We report on haplotype analysis of closely linked markers to the MCKD2 locus in the previously studied families and two additional families. Conclusion. In all five families the association of MCKD2 with the disease was excluded by a multipoint LOD score < -2, thus suggesting the involvement of a third MCKD locus.