Kimberling W J, Fain P R, Kenyon J B, Goldgar D, Sujansky E, Gabow P A
Boys Town National Institute, Omaha, NE 68131.
N Engl J Med. 1988 Oct 6;319(14):913-8. doi: 10.1056/NEJM198810063191405.
Autosomal dominant polycystic kidney disease has been shown to be closely linked to the alpha-hemoglobin complex on the short arm of chromosome 16. We describe a five-generation kindred, descendants of Sicilian immigrants, in which the disease occurs but without linkage to the alpha-hemoglobin complex. DNA probes were used in genetic-linkage studies on blood samples from 163 family members, of whom 71 were affected by or at risk for autosomal dominant polycystic kidney disease. Diagnoses were confirmed by ultrasound examination. In this family the frequency of recombination between the alpha-hemoglobin complex and the region previously shown to contain the mutation causing polycystic kidney disease exceeded 24 percent, indicating a mutation at a different locus. The clinical findings in this family were indistinguishable from those in other families with polycystic kidney disease. We conclude that there is a second gene for autosomal dominant polycystic kidney disease. This apparent heterogeneity means that prenatal and presymptomatic diagnosis must be approached with caution until a method is found to distinguish between the two forms of the disease.
常染色体显性多囊肾病已被证明与16号染色体短臂上的α-血红蛋白复合体紧密相连。我们描述了一个五代家族，其为西西里移民的后代，该家族中出现了这种疾病，但与α-血红蛋白复合体没有连锁关系。对163名家庭成员的血液样本进行了基因连锁研究，其中71人患有或有患常染色体显性多囊肾病的风险，使用了DNA探针。诊断通过超声检查得以证实。在这个家族中，α-血红蛋白复合体与先前显示含有导致多囊肾病突变的区域之间的重组频率超过24%，表明在不同位点发生了突变。这个家族的临床发现与其他患有多囊肾病的家族无法区分。我们得出结论，常染色体显性多囊肾病存在第二个基因。这种明显的异质性意味着在找到区分这两种疾病形式的方法之前，产前和症状前诊断必须谨慎进行。
