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The article discusses the benefits and uses of genetics and genetic testing in the clinical evaluation of cardiomyopathy among individuals and families for improved outcomes. The case of a 24-year-old man with familial cardiomyopathy is highlighted to help identify others in the family who are at a risk of developing the disease.

A study to examine the results of carrier screening of Ashkenazi Jews for gaucher disease (GD) is presented.

The frequency and types of undetected cancer-predisposing mutations in BRCA1, BRCA2, CHEK2, TP53 and PTEN are determined among patients with breast cancer from high-risk families with negative genetic test results for BRCA1 and BRCA2. The analysis shows that around 12% are expected to carry a large genomic deletion or duplication in one of BRCA1 or BRCA2 genes and approximately 5% are expected to carry a mutation in CHEK2 or TP53.

Some women may inherit an increased risk of developing breast or ovarian cancer. This increased susceptibility to breast and ovarian cancer is caused by mutations in the BRCA1 gene located on chromosome 17. Both male and female carriers of the altered form of the BRCA1 gene can be identified by undergoing genetic screening. This type of screening can have a significant affect on the lives of women from families with a high incidence of breast and ovarian cancer. Women from these families often live in fear of developing these types of cancer at a young age. Genetic screening can enable earlier diagnosis of breast or ovarian cancer in women who are carriers of the altered gene. Some individuals who are carriers may choose to undergo a preventative mastectomy or ovariectomy. Insurance companies may be reluctant to pay for this type of screening despite its benefits.

Genetic screening may be an effective method for identifying women at risk for developing breast or ovarian cancer. Some women may have a higher susceptibility to breast or ovarian cancer as a result of mutations in the BRCA1 gene on chromosome 17. These mutations in these women may cause an estimated 85% lifetime risk of developing breast or ovarian cancer. Women with BRCA1 mutations are also more likely to develop breast cancer before the age of 50 than other individuals. Several families have been identified as having a linkage between the development of breast or ovarian cancer and the BRCA1 gene. Genetic analysis has identified several members of one family as probable carriers of the BRCA1 mutation. Individuals who undergo screening for the BRCA1 mutation may require different types of psychological and social support. This type of screening is not yet available on a widespread basis., Efforts are under way to isolate a gene (BRCA1) on chromosome 17912-21. Mutations in this gene predispose women to breast and ovarian cancer. Women with germline mutations in BRCA1 are estimated to have an 85% lifetime risk of developing breast cancer and an increased but as yet undetermined risk of ovarian cancer. It is estimated that one in 200 to 400 American women may be carriers of BRCA1 mutations. We have identified several families that show nkage between breast and/or ovarian cancer and genetic markers that flank BRCA1. It is now possible, within these linked families, to prospectively identify family members likely to be carrying BRCA1 mutations. Because of profound and immediate clinical ramifications, we offered to provide this information to one such extended family. To provide information to this family, we developed a protocol to address the many issues that arise in the delivery of these services. Although testing for BRCA1 mutation carriers is currently limited to very rare families being analyzed for research purposes, this experience presages the complexities of the much larger scale availability of population screening for BRCA1 mutations, which is likely to become a reality in the next few years. (JAMA. 1993;269:1970-1974)

The article discusses the increasing focus being given to age-related macular degeneration (AMD), which is on the rise. Genetic research has helped provide great insights into the predisposition of AMD, which can be of great assistance in helping such people ward off the illness before it happens.

Scientists plan to map the entire human genome - the complete set of genes - within the next few years. This project promises to vastly improve our ability to detect genetic predispositions for many diseases. There are some possible abuses such advances could bring, however. Employers might use genetic tests to identify employees or potential employees at risk for certain diseases and to deny such people jobs. There are a few situations for which such screening might be justified, but it could also lead to unwarranted discrimination. An employer might use genetic screening to identify workers who are predisposed to early disabling disease. This use of genetic screening is not justifiable, particularly since the screening indicates only an increased risk, not a definite likelihood, for certain diseases. Employers might also use the screening in an effort to cut health care costs. Such a policy would not alter society's overall health care costs, it would deny society the benefit of certain individuals' productivity, and it would unduly burden other employers with higher health care costs. Genetic testing for public safety is also of little use. It only identifies possible future risks, not present functioning. An employer might ask for such tests to identify people at risk for exposure to certain elements of a particular job. Again, in most cases, the testing would only identify a possible risk, not a definite outcome. An employer would need to show that a certain genetic test is highly accurate in predicting adverse effects from the particular exposure of the job. It is important that the legal rights of employees be protected and that the use of genetic testing by employers remain extremely limited. (Consumer Summary produced by Reliance Medical Information, Inc.)

Dopamine is a chemical substance that plays an important role in the transmission of certain nerve signals to and from the brain. Abnormalities of the D2 dopamine receptors have been suggested as a cause or a partial cause of some neurological and psychiatric disorders. Previous researchers have reported that a variation of the D2 dopamine receptor gene (DRD2) known as the A1 allele was present at a significantly higher rate in alcoholics than in nonalcoholics. Other studies have reported similar findings, while yet others have reported no association between the A1 allele and alcoholism. To further examine this issue, the allele at the DRD2 gene locus was determined in 44 alcoholics and 68 control subjects. All subjects were white and none were biologically related. The A1 allele was found in 35 percent of the control subjects and in 45 percent of the alcoholic subjects. Differences between alcoholics and controls in overall frequencies of the A1 and A2 alleles at DRD2 were not considered statistically significant. When the subjects in the alcoholic group were further subdivided into groups based on family history of alcoholism, age at onset, and consumption, the prevalence of the A1 allele was not significantly different for any of these subgroups compared with that of the control group. It is concluded that there is no association between the A1 allele of the DRD2 and alcoholism. (Consumer Summary produced by Reliance Medical Information, Inc.)

Dopamine is a chemical substance that plays an important role in the transmission of certain nerve signals. It is thought that abnormalities related to dopamine and its actions could be responsible or partially responsible for some neurological and psychiatric disorders. A few studies have reported an association between alcoholism and the presence of a variation of a gene associated with the expression of the dopamine D2 (DRD2) receptor, labelled the A1 allele. Other studies have not found such an association. These conflicting results could be explainable if the A1 allele is a modifying gene related to alcoholism as opposed to being a gene specifically responsible for alcoholism. To test this hypothesis, the prevalence of the A1 allele in various groups of people was measured. A total of 853 subjects were examined, including 314 healthy control subjects, 147 subjects with Tourette's syndrome (TS), 104 with attention deficit hyperactivity disorder (ADHD), 33 with autism, 104 who were alcoholics, 35 who suffered from posttraumatic stress syndrome, 13 who suffered panic attacks, 17 who had Parkinson's disease, and 10 who were obese. The A1 allele was found in 24.5 percent of the control subjects. It was found in 44.9 percent of subjects with TS, 46.2 percent of subjects with ADHD, 54.4 percent of the autistic patients, and 42.3 percent of the chronic alcoholics The prevalence for all of these groups was significantly greater than that in the control group. The differences in prevalence between the control group and the other groups studied were not statistically different. These results indicate that the A1 allele is related to, but not the direct cause of, a number of neuropsychiatric disorders. (Consumer Summary produced by Reliance Medical Information, Inc.)

The need for inculcating genetic testing in pediatrics is stressed. The knowledge of individual's genome can help the physicians to address the genetic disorders at an earlier stage.

Genetic analysis may help in the early diagnosis and treatment of cardiovascular and other related diseases. Although most heart diseases have multiple causes, including environmental factors, genetic analysis is improving the understanding of the development and progression of diseases. Genetic mutations have been observed in familial long-QT syndrome, Marfan syndrome, DiGeorge syndrome and other defects caused by abnormal gene expression. Familial cardiomyopathies and their prognoses have been associated with changes in the charge of amino acids caused by mutations in chromosomes one, 11, 14 and 15. Approximately 50% of patients with extreme mutations die before the age of 40, while others do not die prematurely. Unfortunately, genetic diagnosis is complicated by wide variation and multiple abnormalities in chromosomal deletions within disease types. Members of a family affected by the same syndrome may have different chromosome abnormalities.

The results from multiple cohort studies related to the link between the allelic variant CYP2C19*2) and other loss-of-function allelic variants of this gene to major adverse cardiovascular syndrome (ACS) in patients taking clopidogel are reviewed. The insights gained from the CYP2C19 genetic testing might be particularly useful in patients at risk of poor outcomes, for those who have either suffered an adverse event (stent thrombosis) or other at-risk characteristics such as diabetes mellitus, chronic renal failure of angiographic high-risk features.

The extensive research on the single-nucleotide polymorphism (SNP) along with genome testing and clinical trials is providing a deeper understanding of the causes of deep vein thrombosis.

Several genetic screening tests exist for cancer and other diseases but it may be a while before this type of screening can be integrated into primary care practice. A 1996 study found that fewer than half of the family members of those with the BRCA1 breast cancer gene mutation wanted to know their test results. People at risk of genetic diseases need comprehensive education and counseling. Many primary care physicians will need to decide who will provide this counseling. They will also be the one who has to explain and interpret the test results.

Scientists have located the gene that causes Huntington's disease. Huntington's disease is a hereditary disorder characterized by progressive degeneration of the central nervous system. The gene was discovered by 58 scientists from the US and the UK who were part of the Huntington's Disease Collaborative Research Group. This gene is called the IT15 gene and is located on the short arm of chromosome 4. The IT15 gene encodes for a newly discovered protein which has been named huntingtin. Huntingtin is different from other proteins that have been described, and its function in the body is unknown. The genetic mutation that causes Huntington's disease is characterized by increased repetition of the CAG nucleotides. Individuals with Huntington's disease have between approximately 42 and 100 CAG repeats near the start of the IT15 gene, compared with 11 and 34 in normal individuals.

The TB Genotyping Information Management System (TBGIMS) was launched by CDC to improve dissemination of data to state and local health officers, including TB controllers. The designed centralized database and reporting system for TB GIMS could help detect suspected tuberculosis outbreaks and thereby direct public health action and response more efficiently.