Clinical Diagnosis And Genetic Testing

Although the diagnosis of FAP relies primarily upon clinical findings in symptomatic individuals, genetic testing is most often used in the early diagnosis of at-risk family members and in the confirmation of the diagnosis of FAP in patients with equivocal findings. Genetic testing is typically run on DNA extracted from white blood cells obtained from a blood sample. Several DNA-based techniques are available for the detection of APC mutations in FAP families (Table 1),[19] including full gene sequencing, mutation scanning by conformation-sensitive gel electrophoresis (CGSE) of exons 1-14 combined with protein truncation testing (PTT) of exon 15, PTT alone, and linkage analysis. Full gene sequencing has the highest estimated mutation detection rate of approximately 95%. Sequence confirmation of familial mutations identified by any technique other than full gene sequencing is highly recommended if the result will be used for predictive testing of at-risk family members. If germline testing reveals a mutation in an individual affected with FAP, the clinical diagnosis is confirmed, and genetic testing of at-risk family members will provide true

Table 1 Molecular genetic testing for FAP

Direct full gene sequencing: Detects APC sequence alteration. Most precise method for mutation detection (~ 95% sensitivity). Time consuming and expensive

Single-strand conformational polymorphism (SSCP) and denaturing gradient gel electrophoresis (DGGE): Rely on difference in the movement of a mutated DNA compared with normal DNA during electrophoresis

The in vitro synthesized protein assay (IVSP), also called protein truncation test (PTT): Detects premature truncation of the APC protein. It is the main test for FAP (~ 80% sensitive)

Confirmation sensitive gel electrophoresis (CSGE) combined with protein truncation testing (PTT): Detects APC sequence alteration and premature truncation of the APC protein (~ 80-90% sensitive)

positive or negative results. Ultimately, if a mutation cannot be identified, further testing of at-risk relatives should not be pursued, because testing will not be conclusive; a negative result could be a false negative because current testing may not be capable of detecting a mutation even if present. Although it is possible to initiate germline testing with an at-risk family member when an affected family member is not available for testing, this strategy can only yield positive or inconclusive results. In this situation, only the identification of a mutation in a family member can enable a true negative result. Genetic testing should always be done in the setting of pre- and post-test genetic counseling, as endorsed by the American Society of Clinical Oncology in its position statement on genetic testing for hereditary cancer.[20] The process of genetic counseling includes providing risk assessment, educating patients about testing options, discussing the implications for medical management, and providing supportive counseling to the individual and their family. Genetic counseling for FAP should be offered to any patient that has personal or family history features suggestive of FAP, and genetic testing should be offered when results could influence the medical management of that patient or the patient's family members.

As colon screening for those at risk for classic FAP begins as early as age 10, genetic testing is offered to children in FAP families as early as age 8. In AFAP families, colon screening for at risk individuals begins at age 18 years, so genetic testing is generally offered at around 18 years of age. Age-appropriate education should be provided to at-risk children during the genetic counseling process, and children should be involved in the decision whether to undergo genetic testing.

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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