Many genetic diseases continue to be detected by the effects they produce in body structure, function, or chemistry. With the elucidation of gene structure and the cataloging of human gene mutations, direct detection of hundreds of mutations is possible. For known genetic disorders for which specific mutational analysis is not available, indirect analysis using varied techniques, including protein expression, may be applicable.
Genetic testing for diagnostic purposes requires patient education and consent, healthcare provider request, and coordination of sample collections. Sensitivity of testing in genetic disease needs to be addressed because many diseases may have different causes, and many genetic tests are not capable of finding all mutations in complex genes. For example, nearly 1000 gene mutations have been linked to cystic fibrosis, but still, an estimated 3%–10% of mutations cannot be found. Interpretation of results can be a challenge also, especially in situations in which a gene change can be demonstrated, but it is not known whether it is a harmless change. An example of this is polymorphism in the BRCA1 gene. In such situations, interpretation may rely on comparison to gene changes found in known affected relatives.
A variety of morbid genetic changes have been discovered, including gain or loss of a single base pair or larger group of base pairs as well as repetitive sequences that get copied over and over so many times that they disable the function of the gene. Detection strategies are tailored to the type of mutation present or suspected.
Establish availability and sensitivity of clinical testing and inform the patient of the benefits, limitations, and consequences of testing (see Genetic Counseling). Informed consent may be required. Prepayment may be required. Test results may take weeks or months.
Obtain samples or specimens of body fluids or tissues as specified by the laboratory. Overnight shipment must usually be arranged.
Improved diagnosis of types of cancer may have therapeutic implications.
Discovery of hereditary disease or cancer may have implications for other family members.
Precise DNA tests can be done for some inherited diseases (e.g., cystic fibrosis, Duchenne and Becker muscular dystrophy, some polycystic kidney diseases).
Paternity identity testing and forensic testing.
Identification of microbes in infectious diseases (e.g., Chlamydia, cytomegalovirus).
Prediction of progression in neuromuscular disorders (e.g., Huntington disease, myotonic dystrophy, cerebellar ataxia).
Identification of comorbid disease risks (e.g., progressive kidney failure in some hearing loss syndromes).
Identification of reproductive risks.
Explanation of miscarriage and stillbirth.
Potential associations with common diseases of aging (e.g., cardiovascular disease, Alzheimer disease).