Clinical Utility of Testing

The genes responsible for many of the leukodystrophies have been cloned and characterized. However, in most instances the mutations in these genes are diverse. Therefore, biochemical diagnoses are still widely used, although molecular testing may be performed for carrier and subsequent prenatal testing. CD, however, occurs at increased frequency in the Ashkenazi Jewish population and screening for a limited number of mutations is feasible. CD population screening of Ashkenazi Jewish individuals...

References

World Health Organization Classification of Tumours, Pathology and Genetics, Tumours of Haematopoetic and Lymphoid Tissues. Lyon, France IARC Press 2001. 2. Nowell PC. Progress with chronic myelogenous leukemia a personal perspective over four decades. Annu Rev Med. 2002 53 1-13. 3. Barnes DJ, Melo JV. Cytogenetic and molecular genetic aspects of chronic myeloid leukemia. Acta Haematol. 2002 108 180-202. 4. Melo JV. The diversity of BCR-ABL fusion proteins...

Patterns of Inheritance

One key use of the carefully collected and verified pedigree is determination of the most likely mode of inheritance of a condition in a family. This will have relevance to assessing recurrence risks, approaches to testing, and in some cases, even prognosis. The concept of patterns of inheritance extends from the work of Gregor Mendel, who in the 17th century described transmission of traits associated with single genetic loci.10 Transmission of human genetic conditions and traits has proven to...

Molecular Basis of Disease

Breast cancer is the most common cancer among women in Western countries, with about 180,000 new cases and 40,000 deaths occurring annually in the United States. Epidemiologic factors consistently associated with breast cancer risk include a family history of breast cancer, breast biopsy features, and hormonal risk factors such as age at menarche, parity, and age at first live birth. After female gender and age, family history of breast cancer is the most significant risk factor. In a...

HER2NEU Molecular Basis

HER2 NEU (C-erbB-2) gene amplification, HER2 protein overexpression, or both, are identified in 10 to 34 of invasive breast cancers.10 The ligand for the HER2 NEU protein receptor has not been identified, and its activation may occur through homo- and heterodimerization with other family members (EGFR, HER3, and HER4). Both morphologic and molecular techniques have been used to measure HER2 NEU status in breast cancer clinical samples (Table 24-1).11 The vast majority of these studies have...

Qualitative Detection HCV Assays

There are currently two FDA-cleared qualitative HCV RNA test kits available for diagnostic use, the Amplicor HCV test v2.0 (Roche) and the Versant HCV RNA qualitative test (Bayer). The Amplicor HCV test v2.0 is based on RT-PCR amplification of a portion of the 5' UTR and has an analytical sensitivity of 50IU ml.65 The test incorporates an internal control to detect PCR inhibitors and deoxyuridine triphosphate (dUTP) and uracil-N-glycosylase in the reaction mixture to prevent false positives due...

The Genetic Family History

The personal and family medical pedigree has evolved from its earliest ancestors in the 15th century to its current form and has become an essential tool in many aspects of the clinical genetics evaluation. Originally used primarily to display relationship information, the pedigree was used for the first time to demonstrate inheritance of traits in the mid-19th century when Pliney Earl published on inheritance of color blindness and Francis Galton described inheritance of artistic ability and...

Hcv Rna Detection and Quantitation

Detection of HCV RNA in serum or plasma by nucleic acid amplification methods is important for confirming the diagnosis of HCV, distinguishing active from resolved infection, assessing the virologic response to therapy, and screening the blood supply. These tests are incorporated into diagnostic algorithms for HCV proposed by the National Institutes of Health,36 the CDC,37 European Association of the Study of the Liver,38 and National Academy of Clinical Biochemistry.39 The detection of HCV RNA...

Available Assays

Prior to 2001, professional recommendations limited CF carrier testing to individuals with a family history and their partners. Testing laboratories offered laboratory-developed assays using standard platforms, including reverse and forward dot blot, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, oligonucleotide ligation assays (OLA), sequence specific primer-polymerase chain reaction (SSP-PCR), various methods for exon scanning, and sequencing....

Preperinatal Setting

The roots of genetic counseling are often traced to prenatal diagnosis and reproductive decision making. Genetic counselors have been assisting women and couples with difficult reproductive choices for more than three decades. Typically, women referred for genetic counseling and prenatal diagnosis during pregnancy are those who are at increased risk of having a child affected by a genetic disorder. The most common indications are advanced maternal age (women > 35 years of age), abnormal...

Bayesian Analysis Used in Risk Modification

When collected pedigrees are used to provide risk assessment, a variety of data may be relevant to the overall assessment. Numerous factors, some listed above, influence the likelihood that a given individual in the family may be affected by the condition in question or may be a carrier of the gene in question. When it is not possible to do direct diagnostic testing for the condition for example, if the causative gene is unknown , when the affected relative is not available for testing, or for...

Non Mendelian Inheritance Patterns

For a summary of non-Mendelian inheritance patterns, see Table 4-3. Chromosome abnormalities can occur sporadically or can be caused by familial transmission of duplications,deletions, or rearrangements that can result in imbalance of genetic material in the offspring.12 Due to the presence of many genes along the segment of chromosome involved, multiple phenotypic effects usually are seen. Risks to offspring of familial cases depend on parent of origin and size and location of the involved...