Orozco L, Friedman K, Chávez M, Lezana J L, Villarreal M T, Carnevale A
Departamento de Investigación en Genética Humana, Instituto Nacional de Pediatría, Mexico City, Mexico.
Am J Med Genet. 1994 Jun 1;51(2):137-9. doi: 10.1002/ajmg.1320510210.
We describe a compound heterozygous delta-F508/delta-I507 cystic fibrosis patient. Molecular analysis by polymerase chain reaction (PCR)-mediated site-directed mutagenesis showed the 219 bp fragment observed in delta-F508 homozygotes. The father showed a delta-F508 heterozygous pattern while the mother and sister showed a normal pattern. There were four possibilities to explain these results: a) the patient was a delta-F508/delta-I507 compound heterozygote, because the delta-I507 allele fails to amplify when analyzed with delta-F508 primers due to a double mismatch between the primers and template; b) uniparental isodisomy; c) nonmaternity; and d) sample processing mix-up. We then tested for the delta-I507 mutation using specific primers with a single base mismatch, and we found that the patient was in fact a compound heterozygote who inherited the delta-F508 mutation from the father and the delta-I507 from the mother. We underscore the need to detect this rare deletion in patients showing a delta-F508 homozygous pattern when one parent, particularly the father, is a noncarrier.
我们描述了一名患有复合杂合性Δ-F508/Δ-I507囊性纤维化的患者。通过聚合酶链反应（PCR）介导的定点诱变进行的分子分析显示，在Δ-F508纯合子中观察到219 bp的片段。父亲表现为Δ-F508杂合模式，而母亲和妹妹表现为正常模式。有四种可能的情况来解释这些结果：a）患者是Δ-F508/Δ-I507复合杂合子，因为由于引物与模板之间的双重错配，当用Δ-F508引物分析时，Δ-I507等位基因无法扩增；b）单亲二体同二型；c）非母系遗传；d）样本处理混淆。然后，我们使用具有单个碱基错配的特异性引物检测Δ-I507突变，结果发现该患者实际上是一名复合杂合子，从父亲那里继承了Δ-F508突变，从母亲那里继承了Δ-I507突变。我们强调，当父母一方（尤其是父亲）为非携带者时，对于表现出Δ-F508纯合模式的患者，有必要检测这种罕见的缺失。
