Abstract-Seventy-one mutations of the low density lipoprotein (LDL) receptor gene were identified in 282 unrelated Italian familial hypercholesterolemia (FH) heterozygotes. By extending genotype analysis to families of the index cases, we identified 12 mutation clusters and localized them in specific areas of Italy. To evaluate the impact of these mutations on the clinical expression of FH, the clusters were separated into 2 groups: receptor-defective and receptor-negative, according to the LDL receptor defect caused by each mutation. These 2 groups were comparable in terms of the patients' age, sex distribution, body mass index, arterial hypertension, and smoking status. In receptor-negative subjects, LDL cholesterol was higher (ϩ18%) and high density lipoprotein cholesterol lower (Ϫ5%) than the values found in receptor-defective subjects. The prevalence of tendon xanthomas and coronary artery disease (CAD) was 2-fold higher in receptor-negative subjects. In patients Ͼ30 years of age in both groups, the presence of CAD was related to age, arterial hypertension, previous smoking, and LDL cholesterol level. Independent contributors to CAD in the receptor-defective subjects were male sex, arterial hypertension, and LDL cholesterol level; in the receptor-negative subjects, the first 2 variables were strong predictors of CAD, whereas the LDL cholesterol level had a lower impact than in receptor-defective subjects. Overall, in receptor-negative subjects, the risk of CAD was 2.6-fold that of receptordefective subjects. Wide interindividual variability in LDL cholesterol levels was found in each cluster. Apolipoprotein E genotype analysis showed a lowering effect of the ⑀2 allele and a raising effect of the ⑀4 allele on the LDL cholesterol level in both groups; however, the apolipoprotein E genotype accounted for only 4% of the variation in LDL cholesterol.Haplotype analysis showed that all families of the major clusters shared the same intragenic haplotype cosegregating with the mutation, thus suggesting the presence of common ancestors. (Arterioscler Thromb Vasc Biol. 2000;20:e41-e52.)

Effects of continuing nursing mode were studied in elderly home patients with chronic renal failure. Eighty five elderly patients with chronic renal failure were randomly divided into an experimental group (41 cases) and control group (43 cases). Patients in the control group were given the conventional discharge guidance and health education, and those in the experimental group were given the continuing nursing implemented by the continuing nursing team. The results showed that the scores on the self-care skills, sense of responsibility, self-concept and health knowledge of patients with chronic renal failure in the experimental group before discharge were significantly improved compared with those after discharge (P<0.01), the indexes of the dimensions in SF-36 scale were not significantly different between the two groups just after the admission (P>0.05), but those on the third month were significantly higher than those at the admission (P<0.05), and the scores of patients on each dimension in the experimental group were higher than those in the control group (P<0.05). Continuing nursing can effectively improve the self-care ability of elderly patients with chronic renal failure, the patients can actively cooperate with the treatment and nursing, thereby effectively controlling the progression of the disease, reducing the patients' suffering and economic burden, and then improving the quality of life of the patients.

The aim of this study was the characterization of mutations of the LDL receptor gene in 39 Italian patients with homozygous familial hypercholesterolemia, who were examined during the period 1994 to 1996. The age of the patients ranged from 1 to 64 years; one third of them were older than 30. Plasma LDL cholesterol level ranged from 10.8 to 25.1 mmol/L. The residual LDL receptor activity, measured in cultured fibroblasts of 32 patients, varied from <2% to 30% of normal and was inversely correlated with the plasma LDL cholesterol level (r=-0.665; P<0.003). The most severe coronary atherosclerosis was observed in those patients with the lowest residual LDL receptor activity (

1 FH is a heterogeneous condition, since at least four classes of functional defects have been observed that disrupt the synthesis, intracellular transport, LDL binding capacity, and internalization of the LDL-receptor complex.2 During the past few years, the availability of cDNA and genomic clones 3 " 5 has made it possible to characterize the mutations of the LDL receptor (LDL-R) gene at the DNA level. A large array of From the Istituto di Patologia Generale (NX., M.G., R.G., R.T., S.C.), Universita di Modena; Cattedra di Gerontologia (A.G., A.C.), Universita di Bologna; Istituto di Terapia Medica Sistematica (MA, S.F.), Universita di Roma "La Sapienza"; and Cattedra di Genetica Medica (D.A.C.) and Servizio Prevenzione Arteriosclerosi (S.B.), Universita di Geneva, Italia.Supported in part by a grant from the Progetto per la Ricerca Sanitaria della Regione Emilia e Romagna and partly by a grant from Squibb Italia, SpA.Address for correspondence: Sebastiano Calandra, MD, Istituto di Patologia Generale, Universita di Modena, Via Campi 287, 41100 Modena, Italy.Received January 4, 1990; revision accepted October 29, 1990. mutations, including deletions, insertions, nonsense, and missense types, have been found so far in various countries and ethnic groups. During the past 2 years, we have undertaken a survey of Italian FH patients through a collaborative study involving several lipid clinics and aimed at investigating the frequency and features of the major structural rearrangements of the LDL-R gene. So far, we have screened 23 unrelated FH families living in various districts of Italy. DNA screening conducted by the use of 10 restriction enzymes allowed us to identify three patients with gross mutations of the LDL-R gene. Qinical and biochemical details of the 23 FH patients as well as the results of DNA screening and restriction fragment length polymorphism haplotype analysis will be reported elsewhere. In the present report, we illustrate the results of the analysis of the three gross mutations. Two of them (one insertion and one deletion) are new mutations. MethodsThe patients included in this study and designated FH-29, FH-30, and FH-44 were selected from a

We analyzed the molecular defect in the lipoprotein lipase (LPL) gene of a young boy from Sardinia who had primary hyperchylomicronemia, pancreatitis, and a complete LPL deficiency in post-heparin plasma. Analysis of LPL gene was performed by using single strand conformation polymorphism (SSCP) and direct sequencing of SSCP-positive region. The proband was homozygous for a C > A transversion in exon 6, which converts the codon for tyrosine at position 302 into a termination codon and eliminates an RsaI restriction site; this allowed the rapid screening of the proband's family members, among whom nine heterozygotes and one additional homozygote were identified. The homozygote was the proband's paternal grandmother who had shown the first clinical manifestation (recurrent pancreatitis) of LPL deficiency at the age of 54 years. LPL mutation carriers showed a mild dyslipidemic phenotype characterized by a reduction of high density lipoprotein-cholesterol (HDL-C) levels, HDL-C/total cholesterol ratio, and low density lipoprotein (LDL) size, associated with a variable increase of triglyceride levels. Five of these carriers were also heterozygotes for beta-thalassemia (Q39X mutation). In these double mutation carriers, plasma HDL-C levels were higher and plasma triglycerides tended to be lower than in carriers of LPL mutation alone. The Tyr302 > Term mutation encodes a truncated protein of 301 amino acids that is probably not secreted by the LPL producing cells. This is the first mutation of LPL gene found in Sardinians.