This trial tests the hypothesis that confirming a clinical diagnosis of familial hypercholesterolemia (FH) by finding a genetic mutation reduces patients' perceptions of control over the disease and adherence to risk-reducing behaviors. Three hundred forty-one families, comprising 341 hypercholesterolemia probands and 128 adult relatives, were randomized to one of two groups: (a) routine clinical diagnosis; (b) routine clinical diagnosis plus genetic testing (mutation searching in probands and direct gene testing in relatives). The main outcome measures were perceptions of control over hypercholesterolemia, adherence to cholesterol-lowering medication, diet, physical activity, and smoking. There was no support for the main hypothesis: finding a mutation had no impact on perceived control or adherence to risk-reducing behavior (all P-values > 0.10). While all groups believed that lowering cholesterol was an effective way of reducing the risk of a heart attack, participants in whom a mutation was found believed less strongly in the efficacy of diet in reducing their cholesterol level (P = 0.02 at 6 months) and showed a trend in believing more strongly in the efficacy of cholesterol-lowering medication (P = 0.06 at 6 months). In conclusion, finding a mutation to confirm a clinical diagnosis of FH in a previously aware population does not reduce perceptions of control or adherence to risk-reducing behaviors. The pattern of findings leads to the new hypothesis that genetic testing does not affect the extent to which people feel they have control over a condition, but does affect their perceptions of how control is most effectively achieved. Further work is needed to determine whether similar results will be obtained in populations with little previous awareness of their risks.
Amelogenesis imperfecta (AI) is a heterogeneous group of inherited disorders of defective enamel formation. The major protein involved in enamel formation, amelogenin, is encoded by a gene located at Xp22.1-Xp22.3. This study investigated the molecular defect producing a combined phenotype of hypoplasia and hypomineralization in a family with the clinical features and inheritance pattern of X-linked amelogenesis imperfecta (XAI). Genomic DNA was prepared from buccal cells sampled from family members. The DNA was subjected to the polymerase chain-reaction (PCR) in the presence of a series of oligonucleotide primers designed to amplify all 7 exons of the amelogenin gene. Cloning and sequencing of the purified amplification products identified a cytosine deletion in exon VI at codon 119. The deletion resulted in a frameshift mutation, introducing a premature stop signal at codon 126, producing a truncated protein lacking the terminal 18 amino acids. Identifying mutations assists our understanding of the important functional domains within the gene, and finding another novel mutation emphasizes the need for family-specific diagnosis of amelogenesis imperfecta.
A chromosome 12-derived marker was seen in each of 3 testicular germ cell tumors that lacked the i(12p). An interesting feature of 2 of the markers was that the major part, including the centromere, of an acrocentric (a #13 and #14, respectively) was translocated onto 12p, resulting in a dicentric. In the third tumor, 13q (translocated onto 12q) was again probably involved in the rearrangement. The findings support the view that the amplification of genes on 12p represents a significant step in the development of germ cell tumors.
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