June K. Lloyd

Familial lipoprotein lipase (LPL) deficiency: a catalogue of LPL gene mutations identified in 20 patients from the UK, Sweden, and Italy.

The aim of this study was to identify mutations in the lipoprotein lipase (LPL) gene in 20 unrelated patients with familial lipoprotein deficiency (FLLD) and to investigate the genotype/phenotype relationship. The previously reported G188E mutation (Monsalve et al., J Clin Invest 86:728–734, 1990) was screened for and found to be present in seven individuals (12/40 alleles). In addition, three patients were heterozygous for the 2.0 kb insertion (Langlois et al., Proc Natl Acad Sci US 86:948–952, 1989). Two approaches were taken for new mutation detection; single‐strand conformation polymorphism and sequencing to identify micro‐mutations in the proximal promoter and exons 1–9 of the LPL gene and Southern blotting to identify gross mutations. Ten different point mutations were found (W86G, A158T, H183Q, G188E, S193R, P207L, L252X, N291S, M301T, L303P). Additionally, a two nucleotide deletion in exon 6 (Δ1006–1007), a six nucleotide deletion in exon 8 (Δ1441–1447), and a silent substitution in the wobble position of codon E118 were identified. In vitro mutagenesis and expression in COS‐B cells suggested that the A158T and S193R substitutions virtually abolished enzyme activity. In analysing the genotype/phenotype relationship, there was no strong association between age at diagnosis, severity of symptoms, lipid levels, and the nature/position of the mutation. Triglyceride levels, however, were higher in compound heterozygotes compared to true homozygotes, possibly reflecting increased instability of heterodimers. Overall, 29 of 40 (72.5%) mutant alleles were identified. Failure to identify the mutation in 11 alleles might reflect the inadequacy of the method or the possibility that mutations lie within regions of the gene not screened in the study because of lack of availability of sequence. Hum Mutat 10:465–473, 1997.

Surface binding and catabolism of low-density lipoprotein by circulating lymphocytes from patients with abetalipoproteinaemia, with observations on sterol synthesis in lymphocytes from one patient

Surface binding of low-density lipoprotein (LDL), degradation of LDL protein and sterol synthesis were investigated in freshly isolated lymphocytes from normal and abetalipoproteinamic human subjects. LDL binding as a function of LDL concentration showed no evidence of the presence of high-affinity binding sites in fresh lymphocytes from either group of subjects. The rate of degradation of LDL protein by lymphocytes from the patients was no greater than that from the normal subjects and, in the fresh lymphocytes of the one patient studied, sterol synthesis was not increased. We conclude that the formation of LDL receptors and the synthesis of sterol in circulating lymphocytes are largely suppressed and that in normal subjects this may be due to the presence of some plasma constituent other than LDL, possibly the apoE protein. This conclusion is discussed in relation to the possible contribution of LDL receptors to the degradation of LDL protein in vivo.

Nutrition and the training of doctors

The rapid growth in medical knowledge over the past few decades has resulted in overcrowding of the medical curriculum and subjects not perceived to be very useful in clinical medicine have tended to lose time to more promising or expanding topics (Anon., 1983). Because nutrition has been, until relatively recently, a neglected area of medical practice it has also been neglected in medical education. The British Nutrition Foundation, concerned that the resurgence of interest in nutrition and its importance in both the prevention and management of many diseases was not being incorporated into the training of doctors, set up a Task Force to survey the current status of courses in nutrition in undergraduate and postgraduate medical training; this paper summarizes the findings which have already been published in a report entitled Nutrition in Medical Education (British Nutrition Foundation, 1983).

Coronary heart disease. The paediatrician's approach to prevention.

URING THE past two to three decades there has been a marked increase in the rate of death from coronary heart disease in all the so-called affluent countries of the world. The increase has been particularly marked in the younger age group (35-44 years) and at all ages is much greater in men than in women. In males coronary heart disease is now the single largest cause of death in Britain and is also an important cause of morbidity. Advances in the management of acute coronary episodes, although of considerable value for the individual, are unlikely to result in a major decrease in the overall mortality and morbidity, which can only come from primary prevention. This should start early in life before the underlying disease process in the coronary arteries (atherosclerosis) has become established.l~2 2

Genetic Evidence that the Apolipoprotein Gene is not Involved in Abetalipoproteinemia

Elevated serum levels of apo B-containing lipoproteins are associated with risk of Ischaemic Heart Disease1, therefore factors controlling apo B synthesis in the liver and intestine are important to our understanding the development of hyperlipidaemia and atherosclerosis. It may be possible to obtain a better idea of the control of apo B synthesis by studying patients with defects in the synthesis and secretion of apo B containing lipoproteins.

Clinical features of lipoprotein disorders

ConclusionsThe clinical features of plasma lipoprotein disorders have already taught us much about the function of lipoproteins, but certain aspects remain unexplained, notably the relationship of lipoprotein deficiency to neurological function. We can still learn more from nature’s experiments than from our own.