Ravine D, Walker R G, Gibson R N, Forrest S M, Richards R I, Friend K, Sheffield L J, Kincaid-Smith P, Danks D M
Murdoch Institute, Royal Children's Hospital, Melbourne, Australia.
Lancet. 1992 Nov 28;340(8831):1330-3. doi: 10.1016/0140-6736(92)92503-8.
It is now clear that mutations of at least two genetic loci can lead to autosomal dominant polycystic kidney disease (ADPKD). We have compared the clinical features of ADPKD caused by mutations at the PKD1 locus (linked to the alpha-globin complex on chromosome 16) with those of disease not linked to the locus (non-PKD1). We identified 18 families (285 affected members) with mutations at PKD1 and 5 families (49 affected individuals) in which involvement of this locus could be dismissed. Non-PKD1 patients lived longer than PKD1 patients (median survival 71.5 vs 56.0 years), had a lower risk of progressing to renal failure (odds ratio 0.35, 95% CI 0.13-0.92), were less likely to have hypertension (odds ratio adjusted for age and family of origin 0.29, 0.11-0.80), were diagnosed at an older age (median 69.1 vs 44.8 years), and had fewer renal cysts at the time of diagnosis. Although most of the PKD1 families were ascertained through clinics treating patients with renal impairment, no non-PKD1 family was identified through this source. Non-PKD1 ADPKD has a much milder phenotype than that linked to PKD1. Partly as a result of this difference in severity, the reported prevalence of this genotype is probably an underestimate.
现在已经明确，至少两个基因位点的突变可导致常染色体显性遗传性多囊肾病（ADPKD）。我们比较了由PKD1位点（与16号染色体上的α-珠蛋白复合体连锁）突变引起的ADPKD与未与该位点连锁的疾病（非PKD1）的临床特征。我们确定了18个在PKD1位点有突变的家系（285名患病成员）和5个可以排除该位点受累的家系（49名患病个体）。非PKD1患者比PKD1患者寿命更长（中位生存期分别为71.5岁和56.0岁），进展为肾衰竭的风险更低（比值比0.35，95%可信区间0.13 - 0.92），患高血压的可能性更小（经年龄和家系校正后的比值比0.29，0.11 - 0.80），诊断时年龄更大（中位年龄分别为69.1岁和44.8岁），诊断时肾囊肿更少。虽然大多数PKD1家系是通过治疗肾功能损害患者的诊所确定的，但没有一个非PKD1家系是通过该来源确定的。非PKD1型ADPKD的表型比与PKD1相关的要轻得多。部分由于严重程度的这种差异，该基因型的报告患病率可能被低估了。
