Scolari F, Ghiggeri G M, Casari G, Amoroso A, Puzzer D, Caridi G L, Valzorio B, Tardanico R, Vizzardi V, Savoldi S, Viola B F, Bossini N, Prati E, Gusmano R, Maiorca R
Division and Chair of Nephrology, Spedali Civili and University, Brescia, Italy.
Nephrol Dial Transplant. 1998 Oct;13(10):2536-46. doi: 10.1093/ndt/13.10.2536.
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.
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.
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.
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.
肾单位肾痨-髓质囊肿病（NPH/MCD）综合征是一组遗传性肾小管间质性肾炎的异质性疾病。最常见的变异型是青少年隐性NPH，其基因座（NPH1）已定位在2号染色体的q13区域。MCD是一种较罕见的显性疾病，通常在生命后期被识别，在许多方面与NPH相似，但仍存在显著的临床差异。关于MCD的染色体定位尚无定论。
对5个MCD家系进行了研究。通过家族史、遗传类型、临床症状和组织学进行诊断推断。使用跨越整个NPH1基因座的标记D2S293、D2S340和D2S160进行多点连锁分析。
对5个家系中的28名受累成员（16名男性；12名女性）进行了MCD诊断。10例患者有组织学诊断；11例有临床诊断；7名已故亲属被诊断为慢性肾炎。诊断年龄范围为8至65岁。少数患者发现肾髓质囊肿。在家族1中，该疾病与高尿酸血症和痛风性关节炎有关。肾病进展在家族内和家族间存在差异，同一家族的成员表现为肌酐轻度升高或终末期肾衰竭。与隐性NPH相关的NPH1基因座被排除与显性MCD的连锁关系。
MCD可能比以前认为的更常见。临床表现的变异性和缺乏组织病理学特征导致诊断不常见。与NPH最显著的临床差异是某些家系的发病年龄以及向肾衰竭进展的延迟。排除与NPH1基因座的连锁关系表明存在一个仍有待定位的MCD致病基因座。
