Wright G D, Hughes A E, Larkin K A, Doherty C C, Nevin N C
Mary G. McGeown Nephrology Unit, Belfast City Hospital.
Q J Med. 1993 Jul;86(7):459-63.
Fifteen families with autosomal dominant polycystic kidney disease were analysed for coinheritance of the disease and DNA markers flanking the PKD1 locus. Eleven families demonstrated linkage to PKD1 markers. Two families were unlinked to the PKD1 locus (non-PKD1) and in two families the markers were uninformative. The clinical features and prognosis of 49 subjects with a PKD1 genotype were compared with 17 non-PKD1 subjects. The age at diagnosis in non-PKD1 subjects (37 +/- 11 years) was significantly later than PKD1 subjects (25 +/- 13 years, p < 0.001). Only two (12%) non-PKD1 subjects presented initially with clinical features of autosomal polycystic kidney disease compared to 27 (55%) of PKD1 subjects (p < 0.002). Hypertension was more common in PKD1 compared to non-PKD1 subjects (29% vs. 12%), as was stage renal failure (25% vs. 6%). Seventy-five percent of non-PKD1 subjects had not developed end-stage renal failure by the age of 54 years compared to only 35% of PKD1 subjects. Most families with autosomal polycystic kidney disease in this population have disease due to mutations at the PKD1 locus. However, the proportion of non-PKD1 families appears to be higher than estimates for other populations. This study also confirms initial reports that subjects with a non-PKD1 genotype have a milder disease with a better prognosis than those with a PKD1 genotype.
对15个常染色体显性遗传性多囊肾病家庭进行了分析，以研究该疾病与多囊肾病1（PKD1）基因座侧翼的DNA标记的共遗传情况。11个家庭显示与PKD1标记存在连锁关系。两个家庭与PKD1基因座不连锁（非PKD1），另外两个家庭的标记无法提供有用信息。将49名具有PKD1基因型的受试者的临床特征和预后与17名非PKD1受试者进行了比较。非PKD1受试者的诊断年龄（37±11岁）明显晚于PKD1受试者（25±13岁，p<0.001）。只有两名（12%）非PKD1受试者最初表现出常染色体显性遗传性多囊肾病的临床特征，而PKD1受试者中有27名（55%）出现该特征（p<0.002）。与非PKD1受试者相比，高血压在PKD1受试者中更为常见（29%对12%），晚期肾衰竭也是如此（25%对6%）。75%的非PKD1受试者在54岁时未发展为终末期肾衰竭，而PKD1受试者中这一比例仅为35%。该人群中大多数常染色体显性遗传性多囊肾病家庭的疾病是由PKD1基因座的突变引起的。然而，非PKD1家庭的比例似乎高于其他人群的估计值。这项研究还证实了最初的报告，即非PKD1基因型的受试者所患疾病比PKD1基因型的受试者症状更轻，预后更好。
