Nephrology Dialysis Transplantation, Vol 13, Issue 10 2536-2546, Copyright © 1998 by Oxford University Press
F Scolari, G Ghiggeri, G Casari, A Amoroso, D Puzzer, G Caridi, B Valzorio, R Tardanico, V Vizzardi, S Savoldi, B Viola, N Bossini, E Prati, R Gusmano and R Maiorca
Background. The nephronophthisis-medullary cystic
disease (NPH/MCD) complex represents a heterogeneous group of hereditary
tubulointerstitial nephritis. The most common variant is juvenile recessive
NPH, for which a gene locus (NPH1) has been mapped on chromosome 2q13. MCD
is a less common dominant condition usually recognized later in life, which
resembles NPH in many aspects, still presenting remarkable clinical
differences. 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. Multipoint linkage analysis was performed by markers D2S293,
D2S340 and D2S160 spanning the entire NPH1 locus. Results.
Diagnosis of MCD was made in 28 affected members (16 males; 12
females), belonging to five families. Histological diagnosis was available
in 10 patients; clinical diagnosis in 11; seven deceased relatives had
diagnosis of chronic nephritis. The age at diagnosis ranged from 8 to 65
years. Renal medullary cysts were found in a minority of patients. In
family 1, the disease was associated with hyperuricaemia and gouty
arthritis. Progression of renal disease presented intra- and extra-family
variability with members of the same family showing mild elevation of
creatinine or terminal renal failure. The NPH1 locus associated to
recessive NPH was excluded from linkage to the dominant MCD.
Conclusions. MCD might be more common than previously
assumed. Variability in clinical presentation and absence of
histopathological hallmarks contribute to make the diagnosis 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 existence of an MCD responsible
locus, still to be mapped. Keywords: gout;
hyperuricaemia; linkage analysis; medullary cystic disease;
nephronophthisis; NPH1 locus
ORIGINAL ARTICLES
Autosomal dominant medullary cystic disease: a disorder with variable clinical pictures and exclusion of linkage with the NPH1 locus
Division and Chair of Nephrology, Spedali Civili and University, Piazza Spedali Civili 1, I-25125 Brescia, Italy; Division of Paediatric Nephrology, G. Gaslini Childrens Hospital, Genova, Italy; Telethon Institute of Genetics and Medicine (TIGEM), S. Raffaele Biomedical Science Park, Spedali Civili, Brescia, Italy; Dialysis Service, Desenzano, Italy; Corresponding author
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