Wright G D, Hughes A E, Larkin K A, Doherty C C, Nevin N C
Mary G. McGeown Nephrology Unit, Belfast City Hospital, UK.
Nephrol Dial Transplant. 1993;8(6):491-4. doi: 10.1093/ndt/8.6.491.
Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations at the PKD1 locus in most families. This locus has been assigned to the short arm of chromosome 16 by linkage analysis. It has been estimated that approximately 5% of families have a disease that does not map to this locus and most of these families have clinical features indistinguishable from the disease caused by PKD1 mutations. We report a large three-generation Caucasian family from Northern Ireland with ADPKD in whom all affected individuals (age range 22-68) were normotensive and only the two eldest had mild renal impairment. Linkage was excluded between the disease and both the alpha-globin gene complex and the microsatellite marker D16S283. This family confirms that phenotypic heterogeneity exists between unlinked families and that certain non-PKD1 mutations cause mild disease expression. Many such individuals may therefore remain undetected and the incidence of families with ADPKD who have non-PKD1 mutations may be greater than previously estimated.
在大多数家族中，常染色体显性多囊肾病（ADPKD）是由PKD1基因座的突变引起的。通过连锁分析，该基因座已被定位到16号染色体的短臂上。据估计，约5%的家族所患疾病并不定位于此基因座，且这些家族中的大多数具有与PKD1突变所致疾病难以区分的临床特征。我们报告了一个来自北爱尔兰的三代白人大家庭，其中所有患病个体（年龄范围为22至68岁）血压正常，仅最年长的两人有轻度肾功能损害。该疾病与α-珠蛋白基因复合体及微卫星标记D16S283之间均排除了连锁关系。这个家族证实了非连锁家族之间存在表型异质性，且某些非PKD1突变会导致疾病表现较轻。因此，许多此类个体可能未被发现，具有非PKD1突变的ADPKD家族的发病率可能比之前估计的更高。
