Witchel S S, Lee P A, Trucco M
Division of Endocrinology, University of Pittsburgh School of Medicine, PA 15213, USA.
Am J Med Genet. 1996 Jan 2;61(1):2-9. doi: 10.1002/(SICI)1096-8628(19960102)61:1<2::AID-AJMG1>3.0.CO;2-1.
Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is a common autosomal-recessive disorder. During our routine genotyping of affected individuals and their relatives using allele-specific oligonucleotide hybridization and single-strand conformational polymorphism analysis, we identified two families each segregating three mutations. In both families, a mutation known to be associated with 21-hydroxylase deficiency was identified in healthy individuals but was not detected in the propositus. The propositus in family 1 was shown to be a homozygous carrier for G at nucleotide 655, which alters the splice acceptor site at exon 3. The propositus in family 2 carried the same splicing mutation on the maternal allele and a gene deletion/conversion on the paternal allele. In both families, other clinically unaffected relatives carried the Q318X mutation in exon 8. If molecular diagnostic studies had been limited to the mutation carried by the propositi, relatives would have been misinformed regarding their status as carriers or mildly affected individuals. The findings in these two families emphasize the high frequency of alleles causing 21-hydroxylase deficiency in the population.
由于21-羟化酶缺乏所致的先天性肾上腺皮质增生症是一种常见的常染色体隐性疾病。在我们使用等位基因特异性寡核苷酸杂交和单链构象多态性分析对受累个体及其亲属进行常规基因分型的过程中，我们发现了两个家系，每个家系都分离出三种突变。在这两个家系中，在健康个体中发现了一个已知与21-羟化酶缺乏相关的突变，但在先证者中未检测到。家系1中的先证者被证明是核苷酸655处G的纯合携带者，这改变了外显子3的剪接受体位点。家系2中的先证者在母本等位基因上携带相同的剪接突变，在父本等位基因上携带基因缺失/转换。在这两个家系中，其他临床上未受累的亲属在外显子8中携带Q318X突变。如果分子诊断研究仅限于先证者携带的突变，亲属关于其作为携带者或轻度受累个体的状态将会得到错误信息。这两个家系中的发现强调了人群中导致21-羟化酶缺乏的等位基因的高频率。
