Mutations prevalence

The disease has been reported from many parts of the world and there are now more than 500 families described. The prevalence of genetically proven disease in the west of Scotland has been reported to be 1.98 per 100 000 adults and the probable mutation prevalence was estimated to be 4.14 (95% Cl, 3.04-5.53) per 100 000 adults (Razvi et al. 2005). 

HAE is transmitted as an autosomal dominant disorder due, in most instances, to alterations of the Cl INH gene. Its prevalence is 1/50,000 [60] however, there is a high incidence of de novo mutations accounting for close to 25% of cases. Thus there may not be a family history to guide evaluation of such patients and it is therefore reasonable to obtain a C4 and Cl INH determination in any patient presenting with recurrent angioedema in the absence of urticaria. 

Transferrin binds iron, transporting it to sites where it is required. Ferritin provides an intracellular store of iron. Iron deficiency anemia is a very prevalent disorder. Hereditary hemochromatosis has been shown to be due to mutations in HFE, a gene encoding the protein HFE, which appeats to play an important role in absorption of iron. 

Todesco, L. etal. (2003). Determination of-3858G->A and-164C->A genetic polymorphisms of CYP1A2 in blood and saliva by rapid allelic discrimination large difference in the prevalence of the -3858G->A mutation between Caucasians and Asians. Eur.. Clin. Pharmacol, 59, 343-6. 

Familial hypercholesterolemia (FH) is an autosomal dominantly inherited disease caused by mutations in the gene for the LDL receptor. Up to now more than 680 distinct mutations, distributed over the entire gene, have been described [42]. Heterozygous FH individuals express only half the number of functional LDL-r and, therefore, have a markedly raised plasma cholesterol and usually present with premature coronary artery disease. Homozygous FH individuals are more severely affected and may succumb before the age of maturity. The prevalence of heterozygous FH is approximately 1 in 500 in Caucasians. 

Toxicity and effectivity studies have often been performed in rodent fibroblast cells containing oncogenic H-Ras. However, prenylation of K-Ras B and N-Ras are not as effectively blocked by the farnesyltransferase inhibitors as H-Ras [48] (see below). Thus normal cells may be less sensitive to these drugs because they express K-Ras 4B and N-Ras. In this context it should be noted that H-Ras mutations are relatively uncommon in human tumors [49]. Rather, the K-Ras gene is the most frequently mutated in solid human cancers, whereas N-Ras is prevalent in leukemias. Thus the preclinical evaluation of the farnesylation inhibitors has yet to be critically re-evaluated for trials in humans. 

Subject variability High intraindividual variability in QTc values (circadian and seasonal variation law of regression to the mean) High interindividual variability in QTc values (males versus females) Unknown prevalence in the general population of subjects carrying silent mutations in the ion channels responsible for cardiac repolarization (these subjects have normal QTc value but reduced repolarization reserve) Variability in the individual metabolic capacity for a given drug... 

The prevalence of a gene mutation or a genetic disorder is the total number of people in a specified group at a given time who have the mutation or disorder. This term includes both newly diagnosed and preexisting cases in people of any age. Prevalence is often written in the form "1 in [a number]" or as a total number of people who have a condition. 

Raida, M., Schwabe, W., Hausler, P., et al. (2001) Prevalence of a common fwint mutation in the dihydropyrimidine dehydrogenase (DPD) gene within the 5 -splice donor site of intron 14 in patients with severe 5-fluorouracil (5-FU)-related toxicity compared with controls. Clin. Cancer Res. 7, 2832-2839. 

Beranova, M., Oliveira, L. M. B., Bedecarrats, G. Y., et al. (2001) Prevalence, phenotypic spectrum, and modes of inheritance of gonadotropin-releasing hormone receptor mutations in idiopathic hypogonadotropic hypogonadism. J. Clin. Endocrinol. Metab. 86,1580-1588. 

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