The application of molecular genetics to antenatal diagnosis of inherited disease

Abstract

There are approximately 700 inherited diseases for which the mutated protein is known; for the great majority of these, the affected gene has been cloned. In every case, this permits an improved understanding of the pathophysiology, as well as presypmtomatic and antenatal diagnosis. Polymerase chain reaction, allows this approach to be pursued routinely at 8-10 weeks of pregnancy by chorion sampling, and it may soon be possible to carry out embryo biopsy at the four to eight cell stage to diagnose inherited disease in-vitro. The most exciting prospect will be diagnosis of the oocyte by analysis of the polar body; it should be possible to fertilise and implant only oocytes which carry the non-mutated sequence. The true value of molecular genetics is now being shown by the identification of previously unknown genes as those which, when mutated, cause cystic fibrosis and muscular dystrophy. Linkage analysis will give way to direct analysis, and mutiplexing allows simultaneous assay of several sequences. It is unclear whether universal screening will become possible; this will depend upon the applicability of methods for non-invasive fetal sampling.