Genetic Conditions

This section gives you information on inheritance patterns and understanding risk. 

What Does It Mean If a Disorder Seems to Run in My Family  

A particular disorder might be described as running in a family if more than one person in the family has the condition. Some disorders that affect multiple family members are caused by gene mutations, which can be inherited (passed down from parent to child). Other conditions that appear to run in families are not inherited. Instead, environmental factors 

It is not always easy to determine whether a condition in a family is inherited. A genetics professional can use a person s family history (a record of health information about a person s immediate and extended family) to help determine whether a disorder has a genetic component. 

Some disorders are seen in more than one generation of a family. 

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A number of genetic diseases that result in defects of tryptophan metabolism are associated with the development of pellagra despite an apparently adequate intake of both tryptophan and niacin. Hartnup disease is a rare genetic condition in which there is a defect of the membrane transport mechanism for tryptophan, resulting in large losses due to intestinal malabsorption and failure of the renal resorption mechanism. In carcinoid syndrome there is metastasis of a primary liver tumor of enterochromaffin cells which synthesize 5-hydroxy-tryptamine. Overproduction of 5-hydroxytryptamine may account for as much as 60% of the body s tryptophan metabolism, causing pellagra because of the diversion away from NAD synthesis. 

Rare forms of DM have been reported and account for 1% to 5% of all diagnosed cases. Causes of these rare forms of DM include specific genetic conditions, surgery, drugs, malnutrition,... 

The most notable medical application of IFN-y relates to the treatment of CGD, a rare genetic condition with a population incidence of between 1 in 250 00 and 1 in 1 000 000. Phagocytic cells of patients suffering from CGD are poorly capable/incapable of ingesting or destroying infectious agents such as bacteria or protozoa. As a result, patients suffer from repeated infections (Table 8.10), many of which can be life threatening. 

The choice of target cells is another point worthy of discussion. In some instances, this choice is predetermined, e.g. treatment of the genetic condition, familial hypercholesterolaemia, would require insertion of the gene coding for the low-density lipoprotein receptor specifically in hepatocytes. 

Genetics Home Reference (GHR) is the National Library of Medicine s Web site for consumer information about genetic conditions and the genes or chromosomes responsible for those conditions. Here you can find a condition summary on isobutyryl-CoA dehydrogenase deficiency that describes the major features of the condition, provides information about the condition s genetic basis, and explains its pattern of inheritance. In addition, a summary of the gene or chromosome related to isobutyryl-CoA dehydrogenase deficiency is provided.2... 

What Information about a Genetic Condition Can Statistics Provide ... 

Some statistical terms are commonly used when describing genetic conditions and other disorders. These terms include ... 

Genetic conditions are not named in one standard way (unlike genes, which are given an official name and symbol by a formal committee). Doctors who treat families with a particular disorder are often the first to propose a name for the condition. Expert working groups may later revise the name to improve its usefulness. Naming is important because it allows accurate and effective communication about particular conditions, which will ultimately help researchers find new approaches to treatment. 

What Are the Different Ways in which a Genetic Condition Can Be Inherited ... 

Some genetic conditions are caused by mutations in a single gene. These conditions are usually inherited in one of several straightforward patterns, depending on the gene involved ... 

In codominant inheritance, two different versions (alleles) of a gene can be expressed, and each version makes a slightly different protein. Both alleles influence the genetic trait or determine the characteristics of the genetic condition. 

Codominant inheritance In codominant inheritance, each parent contributes a different version of a particular gene, and both versions influence the resulting genetic trait. The chance of developing a genetic condition with codominant inheritance, and the characteristic features of that condition, depend on which versions of the gene are passed from parents to their child. 

It is important to note that the chance of passing on a genetic condition applies equally to each pregnancy. For example, if a couple has a child with an autosomal recessive disorder, the chance of having another child with the disorder is still 25 percent (or 1 in 4). Having one child with a disorder does not "protect" future children from inheriting the condition. Conversely, having a child without the condition does not mean that future children will definitely be affected. 

Reduced penetrance probably results from a combination of genetic, environmental, and lifestyle factors, many of which are unknown. This phenomenon can make it challenging for genetics professionals to interpret a person s family medical history and predict the risk of passing a genetic condition to future generations. 

As with reduced penetrance, variable expressivity is probably caused by a combination of genetic, environmental, and lifestyle factors, most of which have not been identified. If a genetic condition has highly variable signs and symptoms, it may be challenging to diagnose. 

The signs and symptoms of some genetic conditions tend to become more severe and appear at an earlier age as the disorder is passed from one generation to the next. This phenomenon is called anticipation. Anticipation is most often seen with certain genetic disorders of the nervous system, such as Huntington disease, myotonic dystrophy, and fragile X syndrome. 

Genomic imprinting is a factor that influences how some genetic conditions are inherited. 

Why Are Some Genetic Conditions More Common in Particular Ethnic Groups ... 

Examples of genetic conditions that are more common in particular ethnic groups are sickle cell anemia, which is more common in people of African, African-American, or Mediterranean heritage and Tay-Sachs disease, which is more likely to occur among people of Ashkenazi (eastern and central European) Jewish or French Canadian ancestry. It is important to note, however, that these disorders can occur in any ethnic group. 

A genetic consultation is a health service that provides information and support to people who have, or may be at risk for, genetic disorders. During a consultation, a genetics professional meets with an individual or family to discuss genetic risks or to diagnose, confirm, or rule out a genetic condition. 

A personal or family history of a genetic condition, birth defect, chromosomal disorder, or hereditary cancer. 

If a person is diagnosed with a genetic condition, the genetics professional provides information about the diagnosis, how the condition is inherited, the chance of passing the condition to future generations, and the options for testing and treatment. 

Hundreds of research studies (clinical trials) are under way to test gene therapy as a treatment for genetic conditions, cancer, and HIV/AIDS. If you are interested in participating in a clinical trial, talk with your doctor or a genetics professional about how to participate. 

The following are organizations that provide support and advocacy for patient with genetic conditions and their families19 ... 

Phenylalanine hydroxylase (PH) which requires tetrahydrobiopterin (BH4) as a cofactor, is defective in cases of phenylketonuria (PKU). This is a rare (prevalence 1 / 15 000 in the United Kingdom) genetic condition characterized by fair complexion, learning difficulties and mental impairment. If PH is either not present in the hepatocytes or is unable to bind BH4 and is therefore non functional, phenylalanine accumulates within the cells. Enzymes in minor pathways which are normally not very active metabolize phenylalanine ultimately to phenylpyruvate (i.e. a phenylketone). To use the traffic flow analogy introduced in Chapter 1, the main road is blocked so vehicles are forced along side roads. Phenylpyruvate is excreted in the urine (phenyl-ketone-uria), where it may be detected but a confirmatory blood test is required for a reliable diagnosis of PKU to be made. 

B. Variable expression arises when the nature and severity of the phenotype for a genetic condition varies from one person to another. 

BIOTECHNOLOGY AND YOUR HEALTH Tests for Genetic Conditions... 

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