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The rate of false positive and false negative results in Australia is unacceptable in screening for multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant inherited tumor syndrome. Screening for hyperparathyroidism by serum calcium estimates and serum parathyroidhormone levels is the usual approach, but with the sequencing of the MEN1 gene complete, genetic screening could be done. Even in those without symptoms partial parathyroidectomy should be carried out when hyperparathyroidism is detected and pancreatic tumors should be resected if they are large or growing rapidly.

A 70-year-old white female presented for an eye examination with a chief complaint of a painless, progressive visual blur in both eyes that had persisted for 18 months. Her last [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/S0002-9343(97)00093-4 Byline: Marc A. Warmuth, Linda M. Sutton, Eric P. Winer Abstract: The identification of genetic mutations thought to be directly responsible for the development of breast cancer represents a major advance in our understanding of this disease. Mutations in BRCA1 and BRCA2 are thought to be responsible for the majority of inherited breast cancer. Although these mutations account for approximately 5% of breast cancer cases, the identification of these genes will have a profound impact on the way patients and their physicians view breast cancer risk. Genetic testing for BRCA1 and BRCA2 mutations is already available. Interpreting results of genetic tests for these mutations is problematic and the clinical management of women carrying these gene mutations is far from straightforward. The purpose of this paper is to review recent developments in the genetic aspects of breast cancer, including genetic testing, to critically review risk factor modification, and to discuss screening and potential prophylactic measures. Author Affiliation: (a) Division of Hematology and Medical Oncology, Duke University Medical Center, Durham, North CarolinaUSA Article History: Received 29 May 1996; Accepted 11 November 1996

Messenger ribonucleic acid (RNA) expression for two beta-adrenergic receptors may be identified and show changes during pregnancy in the pregnant rat uterus. Researchers used quantitative reverse transcriptase-polymerase chain reaction techniques to identify messenger RNA expression for the beta-1- and beta-2-adrenergic receptors in the muscle tissue of the rat uterus. Beta-1-receptor messenger RNA decreased and beta-2-receptor messenger RNA remained steady in the second half of rat pregnancy. Over 90% of the receptors were the beta-2-adrenergic receptor subtype. The techniques may be used to analyze genes in human pregnancy that affect uterine contractility.

A screening test to identify the altered gene thought to be responsible for breast and ovarian cancer is now available. This gene is called the BRCA1 susceptibility gene. Research has shown that more than 90% of the women with ovarian cancer who have an immediate family history of ovarian cancer carry the BRCA1 gene. It may be advisable for women who carry this gene to have their ovaries removed as a preventive measure. However, research has not yet identified the best possible course of action for these carriers.

Inherited abnormalities of the BRCA1 gene appear to be involved in some cases where women develop both breast and ovarian cancer independently. The BRCA1 gene is believed to be an important tumor suppressor gene, but at the time of this investigation, its chromosome was known, but not its precise location. Only indirect investigation of abnormalities within regions of its chromosome could be carried out. Its location has since been pinpointed. Cancerous and normal tissue samples were analyzed from 29 women who developed primary cancers of both breast and ovary. DNA analysis revealed abnormalities of the chromosome containing BRCA1 in 46% of breast cancers, 78% of ovarian cancers, and 38% of both cancers. In all cases where the chromosome was abnormal in both cancers, the same strand of the pair was affected. These cases also tended to be among younger women. These women seem more likely to have an inherited genetic defect.

* Purpose: To review significant advances in the early diagnosis and treatment of medullary thyroid carcinoma in patients with the multiple endocrine neoplasia II (MEN II) syndromes, advances made possible by the application of recently discovered genetic information. * Data Sources: Recently published English-language literature on linkage analysis and DNA analysis in the MEN II syndromes. * Study Selection: Articles on familial and sporadic forms of medullary thyroid carcinoma; pentagastrin-calcitonin determination; and genetic testing. * Data Extraction: information from recent studies on 1) the usefulness and limitations of genetic testing, especially DNA and linkage analysis, in the early diagnosis of the familial form of thyroid carcinoma and 2) the correlation between the results of genetic testing and the results of biochemical screening. * Data Synthesis: Medullary thyroid carcinoma accounts for most of the morbidity and mortality among patients with the familial medullary thyroid carcinoma syndromes. Multiple endocrine neoplasia IIa and IIb and familial medullary thyroid carcinoma are inherited conditions with autosomal dominance and incomplete penetrance. Traditionally, diagnosis of and screening for these conditions have been done using pentagastrin stimulation tests and plasma calcitonin determinations. Recent genetic mapping, however, has assigned the genes responsible for these tumors to the pericentromeric region of chromosome 10. Available data suggest that mutations in exon 10, 11, or 16 of the RET proto-oncogene are responsible for MEN IIa and IIb and familial non-MEN medullary thyroid carcinoma. Thus, genetic testing can identify affected members of a kindred and will probably lead to early thyroidectomy and possible cure for gene carriers. * Conclusions: Early studies confirm the usefulness of DNA analysis in the diagnosis and treatment of patients with familial forms of medullary thyroid carcinoma. We review changes in the diagnosis and treatment of these patients and offer a strategy for operative intervention based on results of genetic testing., Advancements in understanding the genetic mechanisms involved in multiple endocrine neoplasia type II (MEN II) are reflected in new diagnosis and treatment strategies. MEN II is an inherited genetic disorder characterized by tumors of the thyroid, adrenal medulla and parathyroid glands. Children with MEN II are often affected by an aggressive form of medullary thyroid carcinoma. Early diagnosis of MEN II and removal of the thyroid gland can prevent this cancer. Biochemical screening based on calcitonin levels has been useful in early diagnosis, but up to 10% of patients may already have metastatic cancer at diagnosis. The detection of genetic mutations on chromosome 10 introduced the possibility of genetic screening for early diagnosis of MEN II. When the mutation has been identified in a patient, all family members should be screened. Affected persons should have their thyroid glands removed and should be monitored for development of pheochromocytoma (an adrenal medulla tumor) and hyperparathyroidism (excessive activity of the parathyroid glands), two other manifestations of MEN II.

In recent years, advances in laboratory diagnostie tests for celiac disease (CD) have transformed the way the disease is diagnosed and monitored, reducing the number of small bowel biopsies performed [...]

The presence of choroid plexus cysts in the second trimester fetus may be associated with chromosomal abnormalities. A choroid plexus cyst is a type of brain cyst. Amniocentesis is indicated when they are found during ultrasound exam. During a two-year period, 9100 women had second trimester sonograms. One or more choroid plexus cysts were found in 102 (1.1%) fetuses. Four fetuses had multiple congenital anomalies, and three of these had chromosomal anomalies as well. The remaining 98 fetuses appeared normal. Seventy-five of them underwent amniocentesis and chromosomal anomalies were found in four fetuses. The 23 fetuses who had no amniocentesis were all normal at birth. All together, the chromosomal anomaly rate associated with choroid plexus cyst(s) was 1 out of 25. Since this exceeds the 1 in 200 risk of pregnancy loss after amniocentesis as well as the 1 in 126 risk of fetal chromosomal anomaly in a 35-year-old woman, amniocentesis should be offered to women carrying fetuses with choroid plexus cysts.

State and federal law do not prohibit life and health insurance companies from using genetic testing results to grant or deny coverage to applicants. Though technology is not developed to an extent to supply insurers with definitive answers regarding an applicant's future health, many insurers favor technology development to enable them to screen out unhealthy applicants and supply low-cost coverage for low-risk people. A national health care plan would be made all the more necessary should genetic testing become an accepted industry practice and create a large class of uninsured people.

Efficient neonatal screening for phenylketonuria and the availability of complex diets for lifelong use have virtually eliminated severe mental handicap from the disease. Nevertheless, there remains a high risk of [...]

Introduction Cystic fibrosis is a severe, autosomal recessive disease affecting one in 2500 live births in the British population. The clinical expression of cystic fibrosis is variable, although most patients [...]

Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are neuromuscular diseases characterized by progressive muscular weakness leading to increased disability and deformity. They are recessive inherited diseases that are linked to the X chromosome, and are thus passed on from mother to son. The diagnosis of the disease has previously been based on the manifestation of clinical symptoms, levels of creatine kinase in the blood serum, and changes in muscle function. However, the gene that is defective in DMD and BMD has been recently isolated and the protein that the gene encodes has been identified as dystrophin. Dystrophin is thought to be involved in the structure of the muscle fibers. The gene was isolated to the short arm of the X chromosome and the DNA from this area was sequenced, or ordered, and the genes and proteins that are encoded by the genes were analyzed. In over 60 percent of the patients with DMD and BMD, segments of the dystrophin gene were found to be deleted. Most of the deletions were found in a particular region of the gene. In the remaining patients, the defect in the gene was probably due to point mutations. The dystrophin protein was found to be expressed in of all types of muscles tissues, such as skeletal muscle, smooth muscle found in the organs and blood vessels, cardiac muscles, and in the brain and spinal cord. There appear to be at least eight variants of the protein that are expressed in different tissues. In patients with severe DMD, there is no detectable protein produced. The majority of the patients with BMD have a form of dystrophin that is abnormal in size and is present in smaller amounts than normal. Some patients with BMD have a normal sized protein but one that is present in smaller amounts and is nonfunctional. Using DNA probes, the genes of individuals can be analyzed to see they contain the defective gene. Parents can be tested to see if they are carriers of the disease and embryos can be analyzed to see if they will develop muscular dystrophy. However, there is a high incidence of new mutations in the dystrophin gene that occur in the embryo itself. Therefore, genetic screening and termination of embryos with the defective gene will not eliminate DMD. Effective therapies must be developed. Therapeutic approaches being explored include the transplantation of normal muscles cells and replacement therapy with normal dystrophin. (Consumer Summary produced by Reliance Medical Information, Inc.)

Applications of molecular diagnostics in oncology and genetic testing are discussed. Advantages of molecular diagnostics such as time saving and low cost are also presented.

While modern medicine is sometimes accused of providing band-aid treatments for complex disorders, the history of Rh disease represents one of medicine's genuine success stories. When the erythrocyte's rhesus D [...]