THE DIAGNOSIS AND PROGNOSIS OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY-DISEASE
THE DIAGNOSIS AND PROGNOSIS OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY-DISEASE
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DOI：
10.1056/nejm199010183231601
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发表时间：
1990-10-18
影响因子：
158.5
通讯作者：
REEDERS, ST
中科院分区：
文献类型：
--
作者：
PARFREY, PS;BEAR, JC;REEDERS, ST
背景资料：常染色体显性多囊肾病通常是由16号染色体短臂上PKD 1位点的突变基因引起的，但在约4%的患有该疾病的家庭中，它是由基因组中其他地方的未知突变引起的。这两种遗传形式的疾病的自然过程没有很好的特点。研究方法：我们研究了17个常染色体显性多囊肾病家族，比较超声诊断与遗传连锁研究诊断的症状前诊断，并将疾病的临床变异与PKD 1突变是否有关。结果如下：在10个家庭的障碍被发现聚集与PKD 1位点两侧的多态性DNA标记，在2个家庭，它没有，在5个家庭的连锁不能确定。在10个PKD 1突变家系中，46%的30岁以下有50%遗传突变风险的成员患有肾囊肿，而在两个无连锁的家系中，这一比例为11%（P < 0.001）。在PKD 1家族中，所有67例超声诊断均通过连锁推断的基因型确定得到证实。48名成员中有40名（83%）年龄小于30岁，遗传了PKD 1突变，患有肾囊肿。所有27名30岁或以上的遗传突变的成员都患有肾囊肿，这表明该年龄组的假阴性诊断概率不超过0.13（P < 0.05）。 平均值（.+-.在PKD 1家族成员中，终末期肾病发病时的年龄为56.7 ± 1.5岁。1.9年，而69.4 .+-。1.7无连锁关系的家族中有囊肿的成员中，有囊肿的成员中，有囊肿的成员高血压和肾损害发生频率较低，发生在无PKD 1突变的家庭。结论：目前，在大多数有50%常染色体显性多囊肾病风险的人中，成像技术是在症状出现之前达到诊断的唯一模式。在这些人中，在成年早期的阴性超声研究表明，遗传PKD 1突变的可能性很小。在少数遗传了非PKD 1突变的多囊肾患者中，肾衰竭可能发生在生命的相对晚期。
Background: Autosomal dominant polycystic kidney disease is usually caused by a mutant gene at the PKD1 locus on the short arm of chromosome 16, but in about 4 percent of families with the disorder it is caused by unknown mutations elsewhere in the genome. The natural course of the disease in both genetic forms is not well characterized. Methods: We studied 17 families with autosomal dominant polycystic kidney disease to compare presymptomatic diagnosis by ultrasonography with diagnosis by genetic-linkage studies and to relate clinical variation of the disease to whether the PKD1 mutation was implicated. Results: In 10 families the disorder was found to congregate with polymorphic DNA markers flanking the PKD1 locus, in 2 families it did not, and in 5 families linkage could not be determined. In the 10 families with the PKD1 mutation, 46 percent of the members less than 30 years old who had a 50 percent risk of inheriting a mutation had renal cysts, as compared with 11 percent of the members of the two families withiout linkage (P < 0.001). In the PKD1 families, all 67 diagnoses made by ultrasonography were confirmed by determination of the genotype as inferred from linkage. Forty of 48 members (83 percent) less than 30 years old who inherited the PKD1 mutation had renal cysts. All 27 members 30 years old or older who inherited the mutation had renal cysts, suggesting that the probability of a false negative diagnosis did not exceed 0.13 in this age group (P < 0.05). The mean (.+-. SE) age at the onset of end-stage renal disease among members of the PKD1 families was 56.7 .+-. 1.9 years, as compared with 69.4 .+-. 1.7 years among members with cysts in the families without linkage (P = 0.0025). Hypertension and renal impairment were less frequent and occurred later in the families without the PKD1 mutation. Conclusions: At present, in most persons with a 50 percent risk of autosomal dominant polycystic kidney disease, imaging techniques are the only mode of reaching a diagnosis before symptoms appear. In such persons a negative ultrasonographic study during early adult life indicates that the likelihood of inheriting a PKD1 mutation is small. In the few who inherit a non-PKD1 mutation for polycystic kidney disease, renal failure is likely to occur relatively late in life.