From mutations

Multiple channelopathies resulting from mutations in Kir channels are known. 

The conversion of a functional into a pseudogene most frequently results from mutations such as frameshift mutations or deletions. Even though pseudogenes might still have some retained functionality such as promoter-or enhancer-like features, they are usually classified as pseudogenes upon their lack of protein-coding ability. 

In the Long QT Syndrome (LQTS), the repolarization phase of the cardiac muscle is delayed, rendering the heart vulnerable to an arrhythmia known as torsade de pointes. LQTS is associated with five genes encoding ion channels. LQTS type 3 (LQT3) results from mutations of Nav1.5, which cause persistent sodium cunent. In contrast, sodium channel mutations associated with Biugada syndrome reduce the expression level of cardiac sodium channels. 

This rare inherited disorder also results from mutations in the gene encoding bilirubin-UGT, but some activity of the enzyme is retained and the condition has a more benign course than type I. Serum bilirubin concentrations usually do not exceed 20 mg/dL. Patients with this condition can respond to treatment with large doses of phenobarbital. 

Thus, in diseases resulting from mutations of mtDNA, an affected mother would in theory pass the disease to all of her children but only her daughters would transmit the trait. However, in some cases, deletions in mtDNA occur during oogenesis and thus are not inherited from the mother. A number of diseases have now been shown to be due to mutations of mtDNA. These include a variety of myopathies, neurologic disorders, and some cases of diabetes mellitus. 

Various Disorders Result From Mutations in Genes Encoding Proteins Involved in Intracellular Transport... 

Familial hypercholesterolaemia is characterized by a significant elevation in plasma LDL concentration. The basic metabolic defect appears to be abnormal LDL receptor function, arising from mutations in the LDL receptor gene. Several receptor mutations have been identified and hypercholesterolaemia severity as well as the age of onset of ischaemic heart disease has recently been demonstrated to vary according to the type of LDL receptor gene defect (Moorjani et al., 1993). 

Li, S., Crenshaw, E. B., Rawson, E. J., Simmons, D. M., Swanson, L. W and Rosenfeld, M. G. (1990). Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1. Nature 347 528-533. 

The genetic code, modified by selection, represents an adaptation of optimized functions, for example, for the minimisation of coding errors (arising from mutations... 

Graw, J., Brackmann, H.H., Oldenburg, J., Schneppenheim, R., Spannagl, M., and Schwaab, R. 2005. Haemophilia A from mutation analysis to new therapies. Nature Reviews Genetics 6(6), 488-501. 

Other diseases with disruptions in neurofilament organization include diabetic neuropathy and Charcot-Marie-Tooth disease. For these diseases, the disruption of neuro filaments may be a secondary effect as in the case of trembler axons or a direct effect. For example, some forms of Charcot-Marie-Tooth peripheral neuropathy result from mutations in a neurofilament subunit [22, 43]. In most cases, neuronal degeneration is an eventual consequence, but neuronal function may be impaired prior to substantial loss of neurons. Generally, disruptions of neurofilaments have the most severe consequences in large motor neurons, which is consistent with the fact that the largest neurons have the highest levels of neurofilament expression. 

Neuropathies can result from mutations that alter the structure or level of expression of PNS myelin proteins (e.g. overexpression of PMP22 in Charcot-Marie-Tooth syndrome (CMT) type 1A), the metabolism of myelin lipids (e.g. metachromatic leukodystrophy), or the capacity of PNS neurons to support their axons in patients with CMT caused by mutations of KIF1B [4] or NF-L [5, 6]. Both acquired and inherited amyloid neuropathies can result from the deposition of poorly soluble proteins, for example cryoglobulins or mutant transthyretins, in and around endoneurial bloodvessels [7-9]. 

Familial demyelinative/dysmyelinative and axonal neuropathies may also be caused by impaired lysosomal lipid metabolism. Metachromatic leukodystrophy (sulfatide lipidosis) results from mutations of the arylsulfatase A gene, which encodes a lysosomal enzyme required for sulfatide turnover. Myelin is affected in both CNS and PNS, though dysfunction is restricted to the PNS in some patients, and the onset of symptoms can occur at any time between infancy and adulthood. Bone marrow transplantation can slow disease progression and improve nerve conduction velocities [57]. (See in Ch. 41.)... 

Familial amyotrophic lateral sclerosis. Familial amyotrophic lateral sclerosis (FALS) is observed in =10% of all cases, but substantially more ALS cases are suspected to be influenced to some degree by genetic factors [75], Mutations in two genes (SOD1 and ALS2 Table 39-3) have been shown to cause FALS, apart from mutations in tau (MAPT) leading to FTD with parkinsonism and... 

The disease results from mutations within the ATP7B gene on the short arm of chromosome 13 [23, 24]. This gene encodes a protein which appears to be involved in copper transport coupled with the synthesis of ceruloplasmin and other cuproproteins. 

Bessis, A. S., Rondard, P., Gaven, F et al. (2002) Closure of the Venus flytrap module of mGlu8 receptor and the activation process insights from mutations converting antagonists into agonists. Proc. Natl. Acad. Sci. USA 99,11097-11102. 

Mitochondrial inheritance Mitochondria, which are the energy-producing centers inside cells, each contain a small amount of DNA. Disorders with mitochondrial inheritance result from mutations in mitochondrial DNA. Although mitochondrial... 

Several inherited cancer syndromes are also known to result from mutations in proto-oncogenes. An example is given by the RET proto-oncogene. Depending on the type of mutation and on which part of the gene is affected, RET mutations can lead to multiple endocrine neoplasia 2A or 2B or familial medullary thyroid carcinoma. These familial cancers are inherited in autosomal dominant fashion. A second example is the CDK4 proto-oncogene, which when mutated can cause familial melanoma. 

I Coronary heart disease can be caused by mutations in the LDL receptor (familial hypercholesterolemia), inherited cancer syndromes can result from mutations in ... 

Variable Thyroid Phenotypes Result from Mutations... 

Nephrogenic diabetes insipidus (NDI) is characterized by renal tubular resistance to the antidiuretic effect of arginine vasopressin (AVP). NDI may be inherited as an autosomal dominant or X-linked recessive disorder. The autosomal dominant form of NDI results from mutations of the aquaporin 2 gene (AQP2). AQP2 encodes a water channel of the renal collecting duct. Its disruption causes autosomal dominant NDI (113,114) and occasionally recessive forms of the disease. 

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