Rare Disease 2 —
Training activity: 11

Details

Review referrals; analyse, interpret and report the results of testing for Huntington Disease to include:

• diagnostic testing
• presymptomatic testing.

Type

Developmental training activity (DTA)

Evidence requirements

Evidence the activity has been undertaken by the trainee​.

Reflection on the activity at one or more time points after the event including learning from the activity and/or areas of the trainees practice for development.

An action plan to implement learning and/or to address skills or knowledge gaps identified.

Reflective practice guidance

The guidance below is provided to support reflection at different time points, providing you with questions to aid you to reflect for this training activity. They are provided for guidance and should not be considered as a mandatory checklist. Trainees should not be expected to provide answers to each of the guidance questions listed.

Before action

What are the intended outcomes of the training activity?

• How will this activity demonstrate your ability to triage diagnostic and presymptomatic referrals and perform targeted analysis for triplet repeat expansions?
• What fundamental knowledge do you need regarding the PCR-based fragment analysis used to size CAG repeats in the HTT gene?
• Have you reviewed the national and international guidelines for HD testing, particularly the ethical protocols required for presymptomatic testing?
• What technical metrics, such as stutter peak patterns or the use of internal standards, must you monitor to ensure a safe and high-quality service?
• How will you gain an understanding of the current clinical management and supportive treatment options available for HD patients to better inform the clinical team?

What do you anticipate you will learn from the experience?

• What insights do you hope to gain regarding the correlation between repeat size and phenotype, including the concepts of anticipation and reduced penetrance?
• What do you already know about the Huntington Disease CAG repeat ranges (normal, intermediate, reduced penetrance, and full penetrance alleles)?
• How do you anticipate this activity will improve your ability to interpret genomic variants and communicate the unique implications of a presymptomatic result to healthcare colleagues?

What actions will you take in preparation for the experience?

• Will you review previous HD cases or the Standard Operating Procedures (SOPs) for triplet repeat analysis in your laboratory?
• How have you planned to clarify the nuances of the presymptomatic testing pathway compared to diagnostic testing?
• What potential difficulties do you anticipate, such as identifying very large expansions that may fail to amplify or managing borderline results near the pathogenic threshold?
• How do you feel about embarking on presymptomatic testing, given the significant life-altering impact these results have on healthy individuals and their families?
• In what situations (e.g., encountering an intermediate allele or a complex family history) will you seek immediate advice from a senior scientist or clinical lead to ensure accurate interpretation and reporting?

In action

What are you doing?

• How are you currently approaching the analysis of the triplet repeat assay data for Huntington’s disease?
• What is the technical rationale for focusing on the HTT gene using your chosen analysis method?
• What decisions are you making right now to determine if a CAG repeat count falls within the normal, intermediate, reduced penetrance, or full penetrance range?
• Which aspects of the interpretation feel intuitive, and which—such as assessing somatic mosaicism or anticipation—require constant reference to disorder-specific guidelines?

How are you progressing with the activity?

• How effective are your current strategies in identifying pathogenic expansions or unusual repeat patterns?
• What challenges are you encountering in this moment, such as ambiguous repeat sizes near clinical thresholds, stutter peaks complicating sizing, or difficulties distinguishing between alleles?
• What are you learning as the data unfolds regarding unexpected patterns or unusual repeat configurations that may require further investigation?

How are you adapting to the situation?

• Which alternative strategies, such as reviewing the electropherogram or using different sizing algorithms, are you considering to clarify discrepancies?
• How are you identifying the need for immediate guidance if you are uncertain about a result’s clinical significance?
• How are you ensuring your interpretation remains strictly within your professional scope of practice and laboratory protocols when handling atypical or complex results?
• In what ways are you adapting your level of scrutiny based on the referral type, particularly for presymptomatic cases where the ethical and clinical stakes of an error are high?

On action

What happened?

• How would you summarise the key findings and specific repeat sizes or patterns observed for the Huntington’s disease cases you analysed?
• Which clinical ranges (e.g., normal, intermediate, reduced penetrance, or full pathogenic) were the results categorised into based on established guidelines?
• What technical challenges did you notice during the analysis, such as stutter peaks complicating sizing or evidence of somatic mosaicism?
• How did you feel during the process, particularly when managing high-stakes diagnostic or presymptomatic results that have significant life-altering implications?

How has this experience contributed to your developing practice?

• How has this activity improved your ability to distinguish between repeat ranges and your technical understanding of PCR-based fragment analysis?
• In what ways did your ‘reflection-in-action’ (real-time decisions made during analysis) influence the final accuracy and technical quality of your interpretation?
• How did you successfully manage ambiguous results or the need for specific consultation to resolve discrepancies?
• How does mastering these specific interpretations relate to your future requirements as a Clinical Scientist in post-programme practice?

What will you take from the experience moving forward?

• Do you require further practice in differentiating repeat types or a deeper understanding of genotype-phenotype correlations?
• How will you apply this learning to future cases, especially for less common triplet repeat disorders with complex expansion patterns?
• Which specific ‘next steps’—including reviewing national guidelines or exploring recent literature—will you take to consolidate your knowledge?
• What support or resources, such as disease databases, expert mentorship, or specialised analysis platforms, have you identified as necessary for your ongoing professional development?

Beyond action

Have you revisited the experiences?

• How has encountering further examples of CAG repeat ranges since your initial analysis changed or deepened your understanding of HD results?
• In what ways have advancements in triplet repeat testing or new clinical insights influenced your perspective on the cases you previously reviewed?
• How has professional storytelling with senior colleagues regarding borderline HD results provided you with new perspectives on your earlier analyses?
• What overarching themes regarding non-Mendelian inheritance have you identified through a wider review of your reflections across the Adult Genomics module?

How have these experiences impacted your current practice?

• To what extent has your confidence in interpreting fragment analysis data improved, specifically in your ability to identify technical artefacts or unusual electropherogram patterns?
• How has the foundational knowledge of quality control and reference ranges gained from HD testing influenced your wider practice, such as your approach to reviewing Standard Operating Procedures (SOPs)?
• How are you applying the clinical reasoning developed during this activity—especially for results near clinical thresholds—to subsequent, unrelated patient cases?
• In what ways is this learning supporting your preparation for ‘in-person’ assessments (e.g., CBDs or OCEs) involving the communication of sensitive and high-stakes HD results?

How might these contribute to your future practice?

• Which solidified skills, such as the ability to correlate genotype with phenotype and apply established guidelines, will be most vital in your future work in neurogenetics?
• What clear actions for continued development—such as attending specialised workshops or reviewing recent literature—will you take to stay current with advancements in triplet repeat testing?
• How has this experience underscored the importance of a patient-centred approach and your professional responsibility in delivering a safe and high-quality genomic service?

Relevant learning outcomes

#	Outcome
# 1	Outcome Review referrals for patients referred for rare disease genomic testing.
# 2	Outcome Analyse, interpret and report results for diagnostic, presymptomatic and familial/carrier rare disease genomic testing.
# 3	Outcome Perform targeted analysis, whole genome analysis, and chromosomal analysis for patients referred for rare disease genomic testing.
# 4	Outcome Interpret genomic variants to investigate their clinical significance for patients referred for rare disease genomic testing.
# 7	Outcome Employ specialist knowledge of rare disease genomic testing to deliver a safe and high-quality service.
# 8	Outcome Demonstrate appropriate communication skills with healthcare professional colleagues to inform the clinical management of patients referred for rare disease genomic testing.