Genetic testing may sometimes be referred to as just one category, though there are several subcategories used to differentiate different genetic tests.

  • Carrier Testing

    Identifies people who may be carriers of a genetic disorder.


    Identifies people who may be carriers of a genetic disorder.

    Carrier testing is performed to identify individuals who have a gene mutation for a disorder inherited in an autosomal recessive or X-linked recessive manner. Carriers usually do not themselves have symptoms related to the gene mutation. Carrier testing is offered to individuals who have family members with a genetic condition, family members of an identified carrier, and individuals in ethnic or racial groups known to have a higher carrier rate for a particular condition.

    Points to consider:

    • Identifying carriers allows reproductive choices.
    • Genetic counseling and education should accompany carrier testing because of the potential for personal and social concerns.
    • Molecular genetic testing of an affected family member may be required to determine the disease-causing mutation(s) present in the family.
    • In some situations, DNA testing may not be the primary way of determining carrier status.
    • Carrier testing can improve risk assessment for members of racial and ethnic groups more likely to be carriers for certain genetic conditions.
  • Diagnostic Testing

    For individuals with symptoms and a family history of geneti


    For individuals with symptoms and a family history of genetic disorders.

    Diagnostic testing is used to confirm or rule out a known or suspected genetic disorder in a symptomatic individual.

    Points to consider:

    • DNA testing may yield diagnostic information at a lower cost and with less risk than other procedures.
    • Diagnostic testing is appropriate in symptomatic individuals of any age.
    • Confirming a diagnosis may alter medical management for the individual.
    • Diagnostic testing of an individual may have reproductive or psychosocial implications for other family members as well.
    • Establishing a diagnosis may require more than one type of genetic test.
    • DNA testing may not always be the best way to establish a clinical diagnosis.
  • Predictive Testing

    For individuals with no symptoms but with a family history o


    For individuals with no symptoms but with a family history of genetic disorders.

    Predictive testing is offered to asymptomatic individuals with a family history of a genetic disorder. Predictive testing is of two types: presymptomatic (eventual development of symptoms is certain when the gene mutation is present, e.g., Huntington disease) and predispositional (eventual development of symptoms is likely but not certain when the gene mutation is present, e.g., breast cancer).

    Points to consider:

    • Predictive testing is MEDICALLY INDICATED if early diagnosis allows interventions which reduce morbidity or mortality.
    • Even in the absence of medical indications, predictive testing can influence life planning decisions.
    • Because predictive testing can have psychological ramifications, careful patient assessment, counseling, and follow-up are important.
    • Many laboratories will not proceed with predictive testing without proof of informed consent and genetic counseling.
    • Identification of the specific gene mutation in an affected relative or establishment of linkage within the family should precede predictive testing.
    • Predictive testing of asymptomatic children at risk for adult onset disorders is strongly discouraged when no medical intervention is available.
  • Prenatal Testing

    Prenatal testing is performed during a pregnancy to assess t


    Prenatal testing is performed during a pregnancy to assess the health status of a fetus. Prenatal diagnostic tests are offered when there is an increased risk of having a child with a genetic condition due to maternal age, family history, ethnicity, or suggestive multiple marker screen or fetal ultrasound examination. Routine prenatal diagnostic procedures are amniocentesis and chorionic villus sampling (CVS). More specialized procedures include placental biopsy, periumbilical blood sampling (PUBS), and fetoscopy with fetal skin biopsy.

    Points to consider:

    • A laboratory that performs the disease-specific test of interest must be identified before any prenatal diagnostic test procedure is offered.
    • All prenatal diagnostic test procedures have an associated risk to the fetus and the pregnancy; therefore, informed consent is required, most often in conjunction with genetic counseling.
    • In most cases, before prenatal diagnosis using molecular genetic testing can be offered, specific gene mutation(s) must be identified in an affected relative or carrier parent(s).
    • Prenatal testing for adult-onset conditions is controversial. Individuals seeking prenatal diagnosis for these conditions should be referred to a professional trained in genetic counseling for a complete discussion of the issues.
  • Pre-implantation Testing

    Genetic testing for embryos resulting from in vitro fertiliz


    Genetic testing for embryos resulting from in vitro fertilization.

    Preimplantation testing is performed on early embryos resulting from in vitro fertilization in order to decrease the chance of a particular genetic condition occurring in the fetus. It is generally offered to couples with a high chance of having a child with a serious disorder. Preimplantation testing provides an alternative to prenatal diagnosis and termination of affected pregnancies.

    Points to consider:

    • Preimplantation testing is only performed at a few centers and is only available for a limited number of disorders.
    • Preimplantation testing is not possible in some cases due to difficulty in obtaining eggs or early embryos and problems with DNA analysis procedures.
    • Due to possible errors in preimplantation diagnosis, traditional prenatal diagnostic methods are recommended to monitor these pregnancies.
    • The cost of preimplantation testing is very high and is usually not covered by insurance.
  • Choosing a Lab

    GeneTests was created to simplify the search for genetic tes


    GeneTests was created to simplify the search for genetic testing laboratories, which may be difficult to locate. For many diseases, there may be only one laboratory providing genetic testing. U.S. patents have been issued covering diagnostic testing for some genetic disorders. A given laboratory may or may not be the exclusive licensee to such a patent. If there is a choice of laboratories, the following factors should be considered:

    Laboratory Personnel

    Genetics laboratory personnel have two major roles: processing patient samples (technologists), and interfacing with referring clinicians regarding their patients (clinical consultants). Lab personnel, who are usually certified in their specialty, may include lab directors, supervisors, technologists, and genetic counselors.

    Compatibility: The test offered by the laboratory must match the specific clinical need

    • Clinical testing gives a result which can be used in patient care; research testing usually does not. If only research testing is available, the patient or family may choose to defer testing until a clinical test is available.
    • The test methodology must be suited to the testing purpose (e.g., Prader-Willi syndrome can be diagnosed with methylation testing, but other tests are required for recurrence risk counseling).
    • Some diseases are caused by mutations in more than one gene. It is important to be sure that the lab selected is testing the appropriate gene(s).
    • Different kinds of DNA tests are available. The laboratory selected should offer what is most appropriate for a specific clinical situation. For instance:
      • A specific gene mutation (e.g., if the familial mutation has been identified)
      • A panel of mutations (e.g., the Ashkenazi Jewish BRCA1 panel of 3 mutations)
      • The complete gene sequence

    Reliability: Direct contact with the laboratory is needed to assess the laboratory's experience and qualifications

    • Does the laboratory have any other certification? (Laboratories with clinical listings in GeneTests have CLIA certification.)
    • Is the laboratory associated with a reputable company or university?
    • Is the laboratory director board-certified?
    • Is the laboratory's work published in the medical literature?
    • What is the laboratory's experience with the specific test being ordered?

    Ease of Communication

    • What professionals are on staff to help assess the appropriateness of testing, determine the best testing paradigm for the family, and interpret test results?
    • Does the laboratory have information on tests offered and logistics of sample collection and shipping easily available by phone, fax, or Internet?
    • What information is contained in the test result report (e.g., raw data, interpretation, references, sensitivity and specificity information)?

    Geographical Location

    • Some states have restrictions on insurance coverage or, as is the case in New York , additional regulatory restrictions.
    • Samples shipped outside of the U.S. must go through Customs, which requires that hazard identification and a statement of value accompany the sample. Language barriers and time zones can also be an issue.

    Turn-Around Time: Time from sample receipt to test result report may vary

    • Clinical laboratories generally have similar turn-around times for tests performed using the same methodology.
    • A shorter turn-around time is advantageous only when it can be determined that quality control and thoroughness are not compromised.
    • Test results for pregnancy management (prenatal diagnosis) are considered urgent due to restrictions on options late in pregnancy. Pregnancy dating should be included with all prenatal samples.
    • The laboratory should be notified in advance of any sample that is "stat" (rush), as the sample processing may be different.

    Cost: May vary from less than $100 to more than $2000 based on several factors

    • Test methodology. Low complexity tests (e.g., single gene mutation) are less expensive than high complexity tests (e.g., full gene sequencing)
    • Laboratory testing strategy. Some labs test for a large number of mutations all at once; other labs test in stepwise fashion, beginning with the most common mutations.
    • Number of individuals tested. Several family members may need to be tested to obtain a meaningful test result.
    • Contractural agreements. Hospitals, insurers, and laboratories negotiate contracts to set the price of testing and amount of reimbursement.
    • Specimen handling. Some cell types require culturing or other special handling before testing.
    • Additional services. Genetic consultation or counseling is usually recommended and sometimes required before genetic testing is performed. These fees should be considered in the total cost.
  • Pretest Counseling & Informed Consent

    If genetic testing is clinically available and useful for a ...

    If genetic testing is clinically available and useful for a particular patient, the patient needs to understand why it is being offered and its implications for medical management and psychosocial well-being. If a competent patient (or parent/guardian) agrees to the proposed genetic test after full disclosure, this constitutes informed consent. Informed consent may be verbal or written. Some laboratories require written documentation of informed consent. (See sample informed consent form from CompGene.)

    Pretest counseling includes:

    • Assessing the patient's risk perception, expectations and support systems.
    • Explaining the implications of testing vs. not testing for medical management and reproductive options.
    • Describing the methods used to obtain specimens and associated risks.
    • Reviewing test accuracy (sensitivity and specificity).
    • Estimating the chance that the test will be positive based on available information (e.g., family history, clinical symptoms).
    • Discussing any out-of-pocket costs to the patient.
    • Establishing a plan for conveying test results. Depending on the circumstances, results may be given:
      • in person
      • by phone, with or without a follow-up appointment
      • by mail (negative results only)
      • only when positive (e.g., newborn screening)

    Results should be revealed only to the individual tested, or his/her parent or guardian, unless explicit permission has been granted to share results.

    Additional issues relevant in some testing situations:

    • Need to clarify biological relationships (parentage, zygosity) for linkage studies.
    • Potential discrimination in employment, insurability or educational opportunities, especially in predictive testing. (Some states have State genetics laws in place prohibiting genetic discrimination).
    • Results from research testing are not generally available for patient care.
  • Sample Logistics and Supporting Documentation

    Contact the lab directly to ask the following questions:


    Contact the lab directly to ask the following questions:

    What are the sample requirements?

    • Are samples from other family members needed?
    • What specimen type is needed?
    • Does the specimen need to be cultured before shipping?
    • What is the requested amount of specimen? Will less be accepted in hard-to-draw situations?
    • What information should be included on the label?

    What supporting documentation is needed?

    • Does the lab have a speciSample Logistics and Supporting Documentation specific requisition form?
    • What clinical history should be included?
    • Are medical records or test results on family members needed?
    • Is family history needed for test interpretation? A pedigree is an efficient way to show family relationships.
    • Is ethnicity relevant to test interpretation?
    • If crossing international borders, are hazard labels and customs paperwork included?

    How should the sample be transported?

    • What is the correct delivery address?
    • When is delivery accepted?
    • Should the sample be frozen, refrigerated or at room temperature during shipping?
    • Is there a courier to the lab, or is taxicab, mail or overnight shipping required?
  • Test Result Interpretation and Follow-Up

    Test results are provided in writing by the laboratory to th


    Test results are provided in writing by the laboratory to the referring clinician. The details of the lab report vary by lab, but may include:

    • Raw data
    • Clinical interpretation of test result
    • Sensitivity and specificity information
    • References

    The clinician explains the meaning of the test result to the patient and to other family members as needed. Test results and follow-up should be documented in the medical record and a copy made available to the patient. For many conditions, educational materials may be available from patient support organizations.

    Parent support & information:

    For Positive Test Results

    If the test purpose was... The interpretation is... And follow-up includes genetic counseling1 and...
    Diagnostic testing Clinical diagnosis is confirmed Medical management and treatment
    Predictive testing The likelihood of showing disease symptoms is increased Counseling for life planning;
    Medical management if available
    Carrier testing The patient is a carrier Testing offered to partner;
    Prenatal testing offered if indicated
    Prenatal testing A fetus is diagnosed with a specific condition Pregnancy treatment/management or termination
    Newborn screening Disease in a newborn is suggested;

    Carrier status in a newborn may be identified.
    Confirmatory testing; if positive, medical management and treatment

    Carrier testing offered to parents
    1. Genetic Counseling includes discussion of expected course of the disorder; possible interventions; underlying cause; risks to family members; reproductive options; support.

    For Negative Test Results

    If the test purpose was... The interpretation is... And follow-up may include...
    Diagnostic testing Clinical symptoms are unexplained Further testing and/or follow-up genetic consultation
    Predictive testing The likelihood of showing symptoms is decreased Counseling for survivor guilt and long-range life planning;
    No high-risk surveillance needed
    Carrier testing High likelihood that the individual is not a carrier;
    Low risk of having a child affected with the condition in question
    Testing offered to other family members if indicated
    Prenatal testing If fetus was symptomatic (e.g., by ultrasound findings), clinical symptoms remain unexplained and may need further investigation.

    If fetus was not symptomatic, the chance of the condition tested for is very small.
    If fetus was symptomatic, further testing and/or pregnancy management

    If fetus was not symptomatic, no follow-up
    Newborn screening The newborn is not expected to have the condition tested for No follow-up
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