Monogenic disorders

For ethical reasons, children enrolled in these clinical trials have also received standard therapy of enzyme infusions, so the results of these studies have been difficult to interpret and are controversial. Nevertheless, there is some evidence that the ex vivo gene transfer approach may evoke a biological response relevant to the treatment of ADA deficiency. Such interpretations have stimulated efforts to use the ex vivo strategy for other monogenic disorders, such as familial hypercholesterolemia, hemophilia B, and Gaucher s disease. 

More than 5000 monogenic disorders have been linked to DNA alteration at a specific gene locus. Cell and gene therapy, although conceived primarily as a means to correct monogenic disorders, is now recog-... 

Kalantaridou S, Chrousos GP Clinical review 148 Monogenic disorders of puberty. J Clin Endocrinol Metab 2002 87 2481. [PMID 12050203]... 

Mixed hyperlipidemia is one of the most common lipid disorders, but only a minor fraction of the affected patients has a monogenic inherited disease. Most patients with mixed hyperlipidemia have a familial combined hyperlipidemia, a multifactorial disease for which the causative factors are not known. Patients have elevated remnant lipoproteins with elevated triglycerides > 3.0 mmol/1 and total cholesterol > 5.0 mmol/1. Two rare monogenic disorders lead to such a lipoprotein pattern,... 

While defective 11/1HSD I seemed the most likely cause of the disorder, no loss-of-function mutations were found in 1 IjSHSD I in the first patients investigated [61 ]. The cause of the disorder in these cases proved to be mutations in hexose-6-phos-phate dehydrogenase (H6PDH), the enzyme that supplies electrons to the NADPH utilized in oxidoreduction [15]. Later studies have found 11/311814 I mutations in some affected individuals. Thus, there are two monogenic disorders giving rise to a similar phenotype cortisone reductase deficiency caused by lljSHSD I mutations,... 

The genetic contribution to stroke and vascular dementia is important. The underlying genetic defects for several monogenic disorders have already been identified (Joutel et al. 1996). 

Familial homozygous hypercholesterolemia is a rare hereditary monogenic disorder caused by mutations of the LDL receptor gene. Individuals have severe hypercholesterolemia associated with premature atherosclerosis. In a single study, patients were treated with gene therapy... 

While CASR variants contribute to monogenic disorders such as FHH and ADH, common CASR polymorphisms may also account for the observed population variation in calcium response that is a risk factor for a variety of disease susceptibilities. In fact,... 

Clues on the physiological role of neuronal nicotinic receptors come from the identification of a form of human epilepsy that can be caused by mutations in either the a4 or the J32 nicotinic subunits. This rare syndrome, autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), was the first idiopathic epilepsy to be identified as a monogenic disorder (244), and consists of seizures that occur during light... 

The pharmacogenetics approach is very well suited to solve the problems of single-gene (Mendelian or monogenic) disorders. 

Human monogenic disorders that confer predisposition to specific infections... 

Abstract. Human monogenic disorders affecting immunity to infection are increasingly recognized. Most are associated with primary immunodeficiencies, which typically confer predisposition to multiple infectious diseases. We review here the known, atypical monogenic disorders that confer a narrow vulnerability to infection with specific microorganisms in otherwise healthy individuals. These experiments of nature have important immunological and clinical imphcations. 

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