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.