LeRoy B S, Uhrhammer N A, Steere K J, Boehm C D, King R A, Rich S S, Williams P P, Smith S A, de Martinville B
Department of Medicine, University of Minnesota Medical School, Minneapolis.
Am J Med Genet. 1988 Nov;31(3):709-21. doi: 10.1002/ajmg.1320310330.
Currently, molecular methods are the most accurate diagnostic tools for carrier detection and prenatal diagnosis of Duchenne muscular dystrophy (DMD). This report illustrates the value of molecular diagnosis as opposed to previous diagnostic methods, the need for frequent re-evaluations as new methodologies develop, and the necessity for in-depth genetic counseling. In Family 1, the proposita was predicted to be a carrier by an indirect assay (abnormal in vitro muscle ribosomal protein synthesis). DNA analysis using restriction fragment length polymorphisms (RFLPs) indicated that she was not a carrier. She gave birth to a predicted non-affected male, who inherited the gene in question. In Family 2 the proposita, an obligate carrier, was initially evaluated by RFLP analysis. Two pregnancies were monitored by first trimester chorionic villous sampling. Re-evaluation indicated that all affected individuals, including one of the embryos, carried a deletion of the dystrophin gene. The identification of an RFLP within the region containing the deletion allowed unambiguous determination of the carrier status of all individuals.
目前，分子方法是杜氏肌营养不良症（DMD）携带者检测和产前诊断最准确的诊断工具。本报告阐述了分子诊断相对于以往诊断方法的价值、随着新方法的发展进行频繁重新评估的必要性以及深入遗传咨询的必要性。在家族1中，先证者通过间接检测（体外肌肉核糖体蛋白合成异常）被预测为携带者。使用限制性片段长度多态性（RFLP）进行的DNA分析表明她不是携带者。她生下了一个预测无病的男性，该男性继承了相关基因。在家族2中，先证者是一名肯定携带者，最初通过RFLP分析进行评估。通过孕早期绒毛取样监测了两次妊娠。重新评估表明，所有受影响个体，包括其中一个胚胎，都携带肌营养不良蛋白基因的缺失。在包含该缺失的区域内鉴定出一个RFLP，从而能够明确确定所有个体的携带者状态。
