Adult Genetic and Genomic Disorders (SLS422)

15 credits

Aim of this module

This module will provide the trainee with knowledge and understanding of the role and application of genetic and genomic testing in the diagnosis  and management of patients with adult onset genetic and genomic disorders, as well as the implications for other family members.

 

The content for this module will focus on (as exemplars) patients who present with features of: inherited peripheral neuropathies, neurogenetic conditions, hypertrophic and dilated cardiomyopathy, infertility (using cystic fibrosis and chromosome disorders), Fragile X testing for premature ovarian failure, inherited breast cancer and Lynch syndrome, Huntington’s disease, myotonic dystrophy and Friedreich ataxia.

  1. Apply appropriate testing strategies relevant to patients referred for adult onset genetic and genomic disorders.
  2. Perform appropriate level of whole genome analysis for patients with primary infertility.
  3. Perform targeted testing for patients referred with adult onset genetic and genomic disorders.
  4. Investigate the clinical significance of variants using a range of bioinformatics tools following current best practice guidelines.
  5. Interpret and report the range of genetic and genomic testing relevant to these adult onset genetic and genomic conditions.
  6. Perform familial follow up studies including for variants of uncertain clinical significance, showing an understanding of the presence of phenocopies.
Number Work-based learning outcome Title Knowledge
1 1

Select the correct genetic test(s) for the patient samples referred for adult conditions using the following exemplars:

  • Hypertrophic and dilated cardiomyopathies
  • Huntington disease
  • Fragile X (FRAXA)
  • Friedreich ataxia (FA)
  • Cystic fibrosis
  • CMT1A/HNPP
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2 1

Select the correct genetic test(s) for the patient samples referred for adult conditions using the following exemplars:

  • Breast cancer
  • Lynch syndrome
  • Familial adenomatous polyposis (FAP)
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3 2

Perform whole genome analysis for patients referred for infertility.

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4 4,5

Interpret results from chromosomal analysis for patients referred for infertility.

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5 3

Perform a PCR-based test to detect common CFTR mutations.

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6 4,5,6

Analyse, interpret and report on the most common CFTR mutations.

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7 5,6

Interpret FMR1 analysis in relation to premature ovarian failure (POF).

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8 5,6

Analyse and interpret the results of laboratory tests to detect triplet repeat expansions.

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9 4,5

Analyse and interpret the results of next generation sequencing for a panel of genes related to adult onset disorders, e.g. genes associated with breast cancer, Lynch syndrome or cardiomyopathy.

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10 5,6

Analyse and interpret the results for predictive or confirmation testing.

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11 5,6

Prepare a range of reports relevant to the referral reason.

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You must complete
3 Case-based discussion(s)
3 of the following DOPS / OCEs
Assessment Title Type
Analyse chromosomes and use correct nomenclature DOPS
FISH analysis using microscopy DOPS
Processing samples for FISH DOPS
Analyse results of MLPA analysis DOPS
Interpret and report MLPA data DOPS
Perform sequence analysis using relevant software DOPS
Analyse the results of CF testing DOPS
PCR amplification of a triplet repeat DOPS
Perform basic risk calculation DOPS
Analyse results generated by Next Generation Sequencing DOPS
Use bioinformatic tools to interpret the clinical significance of a sequence variant DOPS
Prepare a clinical report for a patient referred with a late onset condition unrelated to cancer DOPS
Prepare a clinical report for a patient referred with a personal and or family history of cancer DOPS
Prepare a clinical report for a patient referred with infertility DOPS
Prepare a clinical report for a patient referred for presymptomatic testing for a late onset condition unrelated to cancer DOPS
Prepare a clinical report for a patient referred for presymptomatic testing for an inherted cancer DOPS
Prepare a clinical report for an adult patient referred with a neuromuscular disorder DOPS
Assess microsatellite results from a colorectal sample for Lynch syndrome DOPS
Participate in an MDT meeting with other healthcare professionals OCE
Take a patient history can be undertaken in virtual patient environment OCE
Discuss patient results with a healthcare professional telephone or in person OCE

Important information

The academic parts of this module will be detailed and communicated to you by your university. Please contact them if you have questions regarding this module and its assessments. The module titles in your MSc may not be exactly identical to the work-based modules shown in the e-portfolio. Your modules will be aligned, however, to ensure that your academic and work-based learning are complimentary.

Learning Outcomes

  1. Explain the clinical presentation and assessment of patients with adult onset genetic and genomic disorders.
  2. Discuss and evaluate the appropriate genetic and genomic laboratory testing strategies for adult patients with genetic and genomic disorders according to current best practice.
  3. Discuss the design, operation and performance of the range of genetic and genomic tests relevant to the investigations.
  4. Discuss and debate the relevant clinical scientific, ethical and legal dimensions.
  5. Describe the purpose and evaluate how integrated working across clinical specialisms supports patient-centred care, including the diagnosis and treatment strategies for patients and their families.

Indicative Content

Clinical presentation and assessment of patients with adult onset genetic and genomic disorders

  • Clinical presentation and types of inheritance, including pedigree analysis
  • Importance of accurate phenotyping

 Appropriate genetic laboratory testing strategies for adult patients with genetic disorders

  • Design, operation and performance of a range of genetic tests
  • The principles of cost effectiveness
  • Laboratory testing pathway including reflex testing
  • Single gene and massively parallel sequencing strategies
  • The relative merits of panel based, whole exome and whole genome analysis
  • Testing methodology including limitations and sensitivity
    • PCR based methods including triplet repeats and methylation and kit based testing
    • Copy number variation detection (e.g. MLPA, chromosomal microarray, FISH and G-band analysis)
    • Sequencing – using all current methods in clinical use
    • Validate and verify results
  • The importance of appropriate internal quality control and external quality assurance
  • Bioinformatics for the processing of large datasets
  • Exclusion testing by linked microsatellite analysis in Huntington disease
  • Importance of turnaround time in the pathway of care
  • Interpret archived results based on older technologies and discuss the implication and limitation of these results for the patient and family

 Clinical scientific, ethical and legal considerations

  • Consent for testing and storage of patient material including deceased patients
  • National guidelines for predictive and presymptomatic testing
  • The importance of counselling, e.g. in predictive testing of late onset disorders such as Huntington disease and the importance of distinguishing between diagnostic and predictive test requests
  • Follow-up management including prenatal testing for subsequent pregnancies
  • Safeguarding vulnerable adults

 Interpretation and reporting of results to include:

  • Analysis and interpretation including the relationship of the genetic alteration to the phenotype
  • Proteomics for the interpretation of variants of uncertain significance
  • Clinical reporting
    • Categories of genetic variation observed within these patient groups
    • The mechanisms of pathogenesis for these disorders including the difference between sporadic and inherited conditions, e.g. breast and colon cancer
    • Diagnostic and prognostic significance of genetic abnormalities found in these groups of patients
    • The use of linkage analysis and the risk of recombination to include Bayesian calculation
    • Use of standardised nomenclature to describe genetic and genomic variation
    • How to critically appraise relevant literature and databases to develop an awareness of the need for any further testing
  • Role of multi-disciplinary team (MDT) meetings to aid interpretation and guidelines such as improving Outcomes Guidance and NICE guidelines