Atrial Septal Defect (ASD): Clinical Features, Diagnosis Study and Treatment

  Genetic Testing 

RATIONALE 

 To assist in the identification of genetic mutations in humans with implications regarding health and treatment decisions; to assist in the identification of pathogenic organisms.

PATIENT PREPARATION 

There are no food, fluid, activity, or medication restrictions unless by medical direction.

NORMAL FINDINGS

 Method: Methods are specific to the study of interest and preferred specimen type. Methods include polymerase chain reaction (PCR), immunohistochemical assay, DNA probe using fluorescence in situ hybridization (FISH), gene amplification using chromogenic in situ hybridization (CISH), and cell culture with karyotyping. Absence of findings consistent with genetic abnormalities related to disease or the ability to metabolize medications normally.

OVERVIEW OF GENETIC TESTING

 (Study type: The facility or testing laboratory should be contacted regarding specimen collection requirements. Possible specimen types include whole blood, buccal samples, and tissue samples; related body system: Multisystem.) Genetic testing has become an important piece of the continuously evolving healthcare model. It is now possible to identify diseases before symptoms appear, predict the likelihood of disease development, and implement lifestyle or therapeutic interventions that will reduce or eliminate the effects of disease. A closer investigation into the nature of disease has sometimes revealed a more complex set of interactions than what was previously understood. While human DNA has similarities, there are also many individual differences. Additionally, numerous factors, such as diet, activity, environment, and stress levels, contribute to variations between one individual and another. These factors in combination with our genetic makeup impact our tendency toward the development of illnesses. Technologies made possible through the accomplishments of the Human Genome Project and a multitude of findings from other collaborative research efforts have resulted in an explosion of diagnostic and prognostic information. The subspecialty of microbiology has been revolutionized by molecular diagnostics. Molecular diagnostics involves the identification of specific sequences of DNA. Molecular methods are used to help identify pathogens that were previously undetectable or inconsistently identified by the culture and biochemical methods available at the time. Molecular methods are also used to examine human samples for genetic disorders that are the result of both simple and complex mutations. Areas of great interest and active development related to genetic testing are in microbiology, virology, oncology, and the development of pharmaceuticals. Diagnostic and biotechnology companies are developing assays to identify gene sequences that code for proteins associated with a specific disease. Notable examples include the following:

• Mutations in the epidermal growth factor receptor (EGFR) gene: The gene encodes a protein (EGFR) associated with many types of cancer, including lung, breast, and colorectal cancer.

• Mutations in the KRAS gene: If mutations are present, specific medications used to treat lung, breast, and colorectal cancers will be rendered ineffective; therefore, other options can more immediately be considered.

• Mutations in the HER2-NEU gene associated with breast cancer: If mutations are present, the cancer risk can be stratified, survival can be predicted, and selection of treatment options can be made.

• Mutations in the BRAF gene: If present, the mutations are used to identify patients, with cancers such as melanoma, who might benefit from treatment with specific drugs that are known to be effective.

• Mutations in the P450 cytochrome series: If present, the mutations are used to predict response to specific drugs some people are poor metabolizers (requiring adjustments to higher doses), and some people are ultrasensitive metabolizers (requiring adjustments to smaller doses).

• Factor V Leiden mutation: If present, this mutation indicates the person has a higher than normal risk for thromboembolism.

• Mutations in the BRCA1 and BRCA2 genes: If present, this mutation indicates the person has a high risk for development of hereditary breast or ovarian cancer. This knowledge provides the opportunity to make informed decisions regarding prophylactic mastectomy or oophorectomy.

Atrial Septal Defect (ASD): Clinical Features, Diagnosis Study and Treatment

New assays are being developed either after an effective therapy for the disease has also been developed or at the same time the treatment is being developed, as companion diagnostics. The cost benefit analysis for the development of companion diagnostics makes a clear case for the simultaneous development of tests and targeted therapies rather than application by trial and error. The companion diagnostics model is based on the development of tests that identify diseases or their related pathways, from genetic expression to production and interaction of proteins, and then to development of specific related therapies that are predicted with confidence to be effective.Precision medicine is the combination of identifying specific knowledge about an individual’s genetic makeup with customized therapeutics or adjustments in lifestyle, for example, genotyping for single nucleotide polymorphisms (SNPs). An SNP, or variation of a single nucleic acid in a DNA sequence, has been identified that causes malfunction of an enzyme needed for the metabolism of warfarin. Identification of this genotype has led to the development of algorithms for safe, tailored dosing and administration based on a patient’s genotype, age, weight or body mass index, and gender. Personalization can also be achieved in the customized production or compounding of pharmaceuticals with respect to the strength or formulation of the medication. Customized pharmaceuticals are being used to address dosing issues revealed by the presence of mutations in the CYP 450 series; adverse drug reactions either by under medication or overmedication are sometimes the result of genetic programming rather than a medication error.Knowledge of genetics assists in identifying those who may benefit from additional education, risk assessment, and counseling. Genetics is the study and identification of genes, genetic mutations, and inheritance. For example, genetics provides some insight into the likelihood of inheriting a medical condition such as sickle cell anaemia. Genes are segments of DNA arranged on chromosomes and are inherited from each parent. Humans normally have 46 chromosomes, or 23 pairs of chromosomes, in each cell: 23 chromosomes are inherited from the mother, and 23 chromosomes are inherited from the father. Twenty-two of the 23 chromosomes inherited from each parent are called autosomes.The 23rd pair of chromosomes is called the sex chromosomes: two X chromosomes (an XX pair) are found in females (one X chromosome from each parent) and an X and a Y chromosome (an XY pair) are found in males (one X from the mother and one Y from the father). Variations in number or structure can be congenital or acquired. Variations can range from a small, single-gene mutation to abnormalities in an entire chromosome or set of chromosomes due to duplication, deletion, substitution, translocation, or another rearrangement. Molecular probe techniques are used to detect smaller, more subtle changes in chromosomes. Chromosomes vary in size and may contain hundreds to thousands of genes. Every gene has a specific location on each of its paired chromosomes. Gene sequences on paired chromosomes are also referred to as alleles, and they may be identical or varied. Identical alleles for a gene are termed homozygous; variable alleles are termed heterozygous. An allele can be demonstrated as either a dominant(represented by a capital letter) or a recessive (represented by a lowercase letter) trait. Since one allele comes from each parent, the possible combinations are DD, Dd, and dd. Expression of an autosomal dominant trait would occur with either DD or Dd; expression of an autosomal recessive trait would occur with dd. Expression of a recessive X chromosome-linked trait would always occur in male offspring because there is only a single X chromosome (the father will have contributed a Y chromosome); expression in female offspring would depend on whether the trait was D or d in the X chromosome contributed by the father. Recessive genes are not weaker than dominant genes; rather, expression of the recessive gene is masked by expression of the dominant gene. Some conditions are the result of mutations involving a single gene, and other conditions may involve multiple genes and/or multiple chromosomes. Sickle cell anemia and cystic fibrosis are examples of autosomal recessive, single-gene disorders. Down syndrome is an example of a chromosome disorder in which the cells have three copies of chromosome 21 (trisomy) instead of the normal two copies. Hemophilia is an example of a recessive sex-linked genetic disorder passed from a mother to male children.Genomic studies evaluate the interaction of groups of genes. The combined activity or combined expression of groups of genes allows assumptions or predictions to be made. As an example, genomic studies measure the levels of activity in multiple genes to predict how they, along with environmental and lifestyle decisions, influence the development Of coronary artery disease, type 2 diabetes, or development and growth of a tumor.

INDICATIONS OF GENETIC TESTING

• Assist in confirming the diagnosis of conditions associated with genetic disorders before or after associated symptoms are manifested.

• Assist in determining drug selection and appropriate dosing on an individual basis.

• Assist in forensic identifications or paternity determinations.

• Assist in monitoring the efficacy of therapeutic interventions.

• Determine the probability of passing a heritable disease to unborn children; discuss prenatal planning 

• Establish a predisposition for the development of certain diseases.

• Identify matches for organ donation.

• Identify the cause of an infectious disease.

• Provide an explanation of death 

(e.g., miscarriage, stillbirth).

• Screen for a genetic disease or condition that may affect an embryo, fetus, or neonate.

Obstetrics and Gynaecology Lecture Notes PDF Download

INTERFERING FACTORS OF GENETIC TESTING

Contraindications

Patients who are not capable of comprehending information presented in the pre-and post-testing genetic counselling sessions. The test should not be performed if the parents of an affected born or unborn child, or if the patient himself or herself, is not emotionally capable of understanding the test results and managing the ramifications of the test results. Written and informed consent, in combination with additional education and a support system, are crucial in order to prepare the patient to make life-altering decisions.

Other considerations

• Proper specimen handling and transport are crucial in order to provide accurate results. The laboratory should be consulted regarding specific instructions prior to specimen collection, especially since tissue specimens are considered irretrievable.

POTENTIAL MEDICAL DIAGNOSIS OF GENETIC TESTING  

CLINICAL SIGNIFICANCE OF RESULTS

• Identification of a condition or disease based on the results of specific genetic testing.

• Identification or disqualification of therapies related to a condition or disease based on the results of specific genetic testing.

NURSING IMPLICATIONS OF GENETIC TESTING

BEFORE THE STUDY: PLANNING AND IMPLEMENTATION

Teaching the Patient What to Expect

➧ Inform the patient this test can assist in assessing for infection or disease using genetic testing.

➧ Review the procedure with the patient. Inform the patient that several tests may be necessary to confirm the diagnosis. 

➧ Explain the type of sample needed for the test and inform the patient that the specimen collection process depends on the type of specimen required for testing. 

➧ Address concerns about pain and explain that there may be some discomfort during specimen collection. (See related studies for specific information.)

Potential Nursing Actions

Make sure a written and informed consent, if required, has been signed prior to specimen collection.

➧ Contact the testing laboratory prior to specimen collection in order to obtain accurate information regarding specimen collection containers, sample volumes, and specific transport instructions.

AFTER THE STUDY: POTENTIAL NURSING ACTIONS

Treatment Considerations

➧ Assist in coping with anxiety associated with test results and provide emotional support if results are positive. 

➧ Provide teaching and information regarding the clinical implications of the test results, as appropriate.

Follow-Up, Evaluation, and Desired Outcomes

➧ Acknowledges contact information provided for counselling services and emotional support.