AUTOSOMAL-DOMINANT MEDULLARY CYSTIC-DISEASE - A DISORDER WITH VARIABLE CLINICAL PICTURES AND EXCLUSION OF LINKAGE WITH THE NPH1 LOCUS

Background, The nephronophthisis-medullary cystic disease (NPH/MCD) co mplex represents a heterogeneous group of hereditary tubulointerstitia l nephritis. The most common variant is juvenile recessive NPH, for wh ich a gene locus (NPH1) has been mapped on chromosome 2q13. MCD is a l ess common dominant condition usually recognized later in life, which resembles NPH in many aspects, still presenting remarkable clinical di fferences. Nothing is known about the chromosome locus of MCD. Methods , Five MCD families were studied. Diagnosis was made by inference from family history, type of inheritance, clinical signs and histology. Mu ltipoint linkage analysis was performed by markers D2S293, D2S340 and D2S160 spanning the entire NPH1 locus. Results. Diagnosis of MCD was m ade in 28 affected members (16 males; 12 females), belonging to five f amilies. Histological diagnosis was available in 10 patients; clinical diagnosis in 11; seven deceased relatives had diagnosis of chronic ne phritis. The age at diagnosis ranged from 8 to 65 years. Renal medulla ry cysts were found in a minority of patients. In family 1, the diseas e was associated with hyperuricaemia and gouty arthritis. Progression of renal disease presented intra- and extra-family variability with me mbers of the same family showing mild elevation of creatinine or termi nal renal failure. The NPH1 locus associated to recessive NPH was excl uded from linkage to the dominant MCD. Conclusions. MCD might be more common than previously assumed. Variability in clinical presentation a nd absence of histopathological hallmarks contribute to make the diagn osis uncommon. The most remarkable clinical difference with NPH is the age of onset in some kindreds and a delayed progression towards renal failure. The exclusion of linkage to the NPH1 locus suggests the exis tence of an MCD responsible locus, still to be mapped.