Adult Genomics —
Training activity: 4

Details

Analyse and interpret the results for a range of triplet repeat expansion disorders for adult patients

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 do you already know about common adult-onset triplet repeat disorders, the genes involved, and the typical repeat ranges associated with different clinical presentations?
• What specific aspects of interpreting triplet repeat results do you want to learn more about (e.g., somatic mosaicism, anticipation, correlation between repeat size and phenotype)?
• What actions will you take in preparation for analysing these results? Will you review the mechanisms of triplet repeat expansions and the specific characteristics of each disorder?
• What possible challenges might you anticipate when interpreting these results (e.g., borderline repeat numbers, technical considerations in PCR-based assays) and how might you handle them?

In action

• What are the specific steps you are currently taking to analyse the triplet repeat assay data for the range of adult-onset disorders (e.g., Huntington’s disease, spinocerebellar ataxias, Friedreich’s ataxia). What specific genes are you focusing on, and why?
• What key decisions are you making right now as you examine the repeat numbers and patterns? For instance, how are you determining if the number of repeats falls within a normal, intermediate, or pathogenic range for each specific disorder?
• What aspects of interpreting these results feel intuitive or based on prior knowledge, and what requires more conscious effort or reference to disorder-specific guidelines and resources (e.g., established repeat ranges, consideration of somatic mosaicism or anticipation)?
• How effective are your current strategies in identifying potential pathogenic expansions or unusual repeat patterns associated with these adult-onset disorders?
• What challenges are you encountering in this moment, such as ambiguous repeat sizes, the presence of stutter peaks, or difficulties in distinguishing between different subtypes of a disorder based solely on repeat size?
• What can you learn from the data as it unfolds? Are there any unexpected findings or patterns emerging that you need to investigate further (e.g., unusual repeat configurations)?
• Are there alternative analysis or interpretation approaches you could consider if your initial assessment is unclear or if you encounter discrepancies
• What immediate support or guidance might you need if you are uncertain about a specific result or its clinical significance, particularly for less common triplet repeat disorders? Would it be beneficial to consult with a colleague or refer to specific disease databases?
• Are you ensuring that your interpretation remains within the scope of established laboratory protocols and your level of training and ability, especially regarding the reporting of complex or atypical results?

On action

• For each of the triplet repeat disorders you analysed (e.g., Huntington’s disease, spinocerebellar ataxias, Friedreich’s ataxia), what were the observed repeat sizes or patterns?
  • Did the results fall within normal, intermediate, or pathogenic ranges according to established guidelines?
  • Were there any unusual or challenging aspects to the data, such as stutter peaks or potential somatic mosaicism?
• Did you improve your ability to distinguish between normal, intermediate, and pathogenic repeat ranges for different triplet repeat disorders?
  • Did you gain a better understanding of the technical considerations involved in analysing triplet repeat assays?
• What further learning or refinement is needed in your interpretation of triplet repeat expansion assays for adult-onset disorders?
  • How will you apply this experience to future analyses, particularly for less common triplet repeat disorders or complex cases?
  • What resources or guidelines will you consult to further enhance your expertise in this area?
  • Are there any specific challenges you encountered that you need to seek further guidance on?

Beyond action

• Think back to the specific triplet repeat disorder results you analysed (e.g., Huntington’s disease, spinocerebellar ataxias, Friedreich’s ataxia). Have you encountered further examples of these or other triplet repeat disorders?
• Consider any advancements in the understanding or testing of these disorders that you have learned about since this training activity. How does this new knowledge affect your understanding of the cases you previously reviewed?
• Have you had opportunities to discuss the interpretation of challenging triplet repeat results with senior colleagues or at relevant meetings? Did this offer any new perspectives on your earlier analyses?
• How has your confidence in interpreting triplet repeat assay results for adult patients changed since this training activity?
• Are you now more adept at identifying potential technical artefacts or unusual patterns in the data? Can you recall specific learning points from this training activity that contributed to this?
• Have you been involved in reporting these types of results? How did your experience in this training activity influence your reporting practices?
• What foundational knowledge about triplet repeat disorders and their analysis did you solidify through this training activity that will support your future work in neurogenetics or other relevant areas?
• How has this experience highlighted the importance of adhering to established guidelines and reference ranges in the interpretation of these complex assays?
• What ongoing learning strategies will you employ to stay current with the evolving knowledge in this rapidly advancing field?

Relevant learning outcomes

#	Outcome
# 2	Outcome Perform molecular analysis for patients referred with adult-onset disorders.
# 4	Outcome Interpret genomic variants, including copy number and structural changes and investigate the clinical significance of variants using bioinformatic tools using best practice guidelines.