The genes for most of the a~o l i~o~r o t e i n s . enzymes. and accurate and simple screening for carriers of thalassemia receptors that are involved in lipid metabolism have now been (old JM, varawa1la NY, weatherall DJ: L~~~~~ 2:834-cloned, and their DNA sequence and arrangement of introns 837, 1990) to the use of preimplantation diagnosis of and exons determined and published (reviewed in 1 and 2). The embryos at risk for Untreatable congenital defects (Monk expression of these genes is very complex and must be M, ~~l d i~~ C: L~~~~~ 1: [985][986][987][988] 1990) and the develop-coordinated in response to a number of environmental chalment of gene therapy for treatment of disorders such as lenges, rapidly in the postprandial state and more slowly in adenosine deaminase deficiency (Sharp D: Lancet 1~1277-adaptation to hormonal changes, for example, at puberty or 1278, 1991). These same molecular techniques have also during pregnancy. Molecular details of these control Processes been applied to pediatric lipid disorders with some notable are not yet fully understood, but excellent Progress has already successes, both in their diagnosis and understanding the been made (3). Taken together, this information provides the mechanisms of the resulting pathology, including the recent framework for the identification of the mutations occumng in experiments (wilson JM, G~~~~~~~ M, wu CH, chow-different patients with pediatric lipid disorders. dhury NR, wu GY, chowdhury JR: J ~i~l them 267:963-Several methods have been published that allow rapid com-967,1992) that have led to proposals to treat homozygous paison the sequence specific fragments DNA familial ~yperc~o~estero~emia by gene therapy. ~h~ pur-different individuals amplified in vitro by PCR (4). The first uses pose of this review is to detail this molecular genetic chemical cleavage of mismatched bases in the duplex formed progress for two of the disorders that result in disturbed between two heterologous DNA fragments after hybridization triglyceride metabolism in infants, lipoprotein lipase defi-(5). This is a slow but robust technique that has been used ciency and apo CII deficiency, and four disorders that lead ~U C C~S S~U~~Y to look for mutations in the apo B gene (6). ~e c a u s e to disturbed cholesterol levels in infancy, abetalipoprotein-it is based on chemical methods, the technique is able to detect emia, hypo~eta~ipoproteinemi~ familial defective ape B, all mismatched bases irrespective of sequence (7). and individuals and familial hypercholesterolemia. We will also address Can be identified who are heterozygous for any sequence differthe question of how knowledge of the mutation causing the ence compared with the normal "probe" DNA, which is radiodefect in a particular patient could be clinically useful and labeled with "P deoxycytidine triphosphate. Fragments of DNA highlight areas of research for the future. (Pediatr Res 34: of about 500-600 bp give good results. but for longer fragments [403][404][405][406][407][408][409][410][411][412][413][414...