Bear J C, Parfrey P S, Morgan J M, Martin C J, Cramer B C
Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Am J Med Genet. 1992 Jun 1;43(3):548-53. doi: 10.1002/ajmg.1320430309.
We evaluated the accuracy of ultrasonographic diagnosis of autosomal dominant polycystic kidney disease (ADPKD) and factors influencing its prognosis in members of 17 Newfoundland families originally described in 1984. In 10 families showing genetic linkage between ADPKD and markers for the PKD1 locus, rates of false negative ultrasonographic diagnosis are estimated as 36% below the age of 10 years and 8% or less thereafter, comparable with findings of genetic linkage studies of a subset of family members. At ages above 30 years, false negative ultrasonographic diagnosis of PKD1 disease is unlikely. In 2 families in which ADPKD is not co-inherited with PKD1 markers, only 11% of members aged less than 30 years had kidney cysts. The mean (SE) age of onset of ESRD is 56.3 (1.8) years for persons with the PKD1 form of ADPKD, and 68.7 (1.7) years for affected members of families in which ADPKD is not co-inherited with PKD1 markers (P = 0.01). In the PKD1 families, age of onset of end stage renal disease (ESRD) was unrelated to the sex of the affected individual but was earlier in persons inheriting the disease from their mothers than from their fathers (50.5 vs. 64.8 years, P = 0.004), consistent with an influence of genetic imprinting on disease progression. In females with a PKD1 mutation, onset of ESRD was not influenced by parity. In PKD1 families, resemblance in age of onset of ESRD was apparent; variation was less within than between families (F = 13.0, P less than 0.0001), and risk of false negative ultrasonographic diagnosis appears largely restricted to families in which ESRD occurs relatively late.
我们评估了超声诊断常染色体显性多囊肾病（ADPKD）的准确性，以及影响1984年最初描述的17个纽芬兰家族成员预后的因素。在10个显示ADPKD与PKD1位点标记存在遗传连锁的家族中，超声诊断假阴性率在10岁以下估计为36%，之后为8%或更低，这与部分家族成员的遗传连锁研究结果相当。在30岁以上，PKD1疾病的超声诊断假阴性不太可能出现。在2个ADPKD与PKD1标记不共遗传的家族中，年龄小于30岁的成员只有11%有肾囊肿。ADPKD的PKD1型患者终末期肾病（ESRD）的平均（SE）发病年龄为56.3（1.8）岁，ADPKD与PKD1标记不共遗传的家族中受影响成员的平均发病年龄为68.7（1.7）岁（P = 0.01）。在PKD1家族中，终末期肾病（ESRD）的发病年龄与受影响个体的性别无关，但从母亲遗传该疾病的人比从父亲遗传的人发病更早（50.5岁对64.8岁，P = 0.004），这与遗传印记对疾病进展的影响一致。在携带PKD1突变的女性中，ESRD的发病不受生育次数影响。在PKD1家族中，ESRD发病年龄的相似性很明显；家族内部的差异小于家族之间（F = 13.0，P小于0.0001），超声诊断假阴性风险似乎主要限于ESRD发病相对较晚的家族。
