Sinnott P J, Costigan C, Dyer P A, Harris R, Strachan T
University Department of Medical Genetics, St. Mary's Hospital, Manchester, UK.
Hum Genet. 1991 Jul;87(3):361-6. doi: 10.1007/BF00200920.
We have analysed fifteen classical 21-hydroxylase deficiency families from throughout Southern Ireland and report the serologically defined HLA-A, HLA-B, HLA-Cw, HLA-DR, C4A and C4B polymorphisms that characterize the inferred disease haplotypes. Additionally, we have used a combination of short and long range restriction mapping procedures in order to characterize the CYP21/C4 gene organization associated with individual serologically defined haplotypes. The results obtained indicate that disease haplotypes are characterized by a high frequency (33%) of CYP21B gene deletion and 8 out of 10 such deletion haplotypes are represented by the extended haplotype HLA-DR1, C4BQo, C4A3, HLA-B40(w60), HLA-Cw3, HLA-A3. Large scale length polymorphism in the CYP21/C4 gene cluster was found to conform strictly to a variable number of tandem repeats model with 4 alleles being detected. Disease haplotypes in which defective CYP21B gene expression is inferred to result from pathological point mutations show extensive diversity of associated HLA markers and include two examples of the extended HLA haplotype HLA-DR3, B8, Cw7, A1 haplotype, which has previously been reported to be negatively associated with 21-hydroxylase deficiency. One unusual disease haplotype has two CYP21 + C4 units, both of which appear to contain CYP21B-like genes.
我们分析了来自爱尔兰南部各地的15个经典21-羟化酶缺乏症家族，并报告了血清学定义的HLA-A、HLA-B、HLA-Cw、HLA-DR、C4A和C4B多态性，这些多态性表征了推断的疾病单倍型。此外，我们使用了短程和长程限制性图谱分析方法的组合，以表征与个体血清学定义的单倍型相关的CYP21/C4基因组织。获得的结果表明，疾病单倍型的特征是CYP21B基因缺失的频率很高（33%），10个此类缺失单倍型中有8个由扩展单倍型HLA-DR1、C4BQo、C4A3、HLA-B40（w60）、HLA-Cw3、HLA-A3代表。发现CYP21/C4基因簇中的大规模长度多态性严格符合可变数量串联重复模型，检测到4个等位基因。推断缺陷性CYP21B基因表达是由病理性点突变导致的疾病单倍型显示出相关HLA标记的广泛多样性，包括扩展HLA单倍型HLA-DR3、B8、Cw7、A1单倍型的两个例子，此前曾报道该单倍型与21-羟化酶缺乏症呈负相关。一种不寻常的疾病单倍型有两个CYP21 + C4单位，两者似乎都含有CYP21B样基因。
