Rare Disease 2 —
Training activity: 3

Details

Review referrals; analyse, interpret and report the results of testing for Duchenne Muscular Dystrophy or Becker Muscular Dystrophy (DMD/BMD) to include:

• Diagnostic testing
• Carrier/familial 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 referrals and perform targeted dosage analysis for both diagnostic and carrier cases?
• What specific knowledge do you need regarding the dosage analysis techniques (e.g., MLPA or NGS-based dosage) used in your laboratory to detect deletions and duplications in the DMD gene?
• Are you familiar with the national guidelines and the reading frame rule used to predict whether a deletion/duplication will result in a Duchenne (DMD) or Becker (BMD) phenotype?
• What QC metrics (e.g., probe ratios, standard deviations) are essential to monitor to ensure the data is robust for a clinical report?
• How does the specific location of a deletion or duplication (the precise breakpoints) inform eligibility for modern treatment options, such as exon-skipping therapies?

What do you anticipate you will learn from the experience?

• What insights do you hope to gain regarding the genomic architecture of the DMD locus and the complexities of interpreting large rearrangements?
• Think about what you already know regarding the X-linked inheritance of DMD/BMD and the expected patterns of results in affected males versus female carriers.
• How do you anticipate this activity will improve your ability to correlate genotypes with clinical phenotypes and communicate these findings to healthcare professional colleagues?

What actions will you take in preparation for the experience?

• Will you consult resources on DMD/BMD genetics and testing methodologies? Will you review the National Genomic Test Directory for the appropriate testing pathways?
• Have you planned to discuss the interpretation of complex dosage results?
• What potential difficulties do you anticipate, such as identifying precise breakpoints or handling results in female carriers who may have skewed X-inactivation or be ‘manifesting carriers’?
• How do you feel about the professional responsibility of reporting results that have significant diagnostic and familial implications, particularly regarding recurrence risk and the need for familial testing?
• In what situations (e.g., a complex rearrangement not following the reading frame rule or a novel point mutation) will you seek immediate advice from a senior scientist to ensure you are delivering a safe and high-quality service?

In action

What are you doing?

• What specific steps are you currently taking to analyse the targeted genomic dosage data for the DMD gene?
• Why have you chosen this particular method (e.g., MLPA or NGS-based dosage) or sequence of steps for this analysis?
• What decisions are you making right now as you assess the copy number? For instance, how are you determining the presence or absence of deletions or duplications across the 79 exons of the DMD gene?
• What aspects of this interpretation feel intuitive based on your prior experience, and what requires more conscious effort, such as applying the reading frame rule to predict the clinical phenotype?

How are you progressing with the activity?

• How effective are your chosen methods in allowing you to identify and characterise relevant dosage changes for both diagnostic (affected males) and carrier (females) referrals?
• What challenges are you encountering in this moment? Are you facing difficulties such as:
• Interpreting results with borderline copy number changes?
• Identifying potential carrier status in female relatives where dosage changes may be more subtle?
• Distinguishing between different types of rearrangements or identifying precise breakpoints?
• What can you learn from the data as it unfolds? Are there any unexpected findings, such as an out-of-frame deletion in a patient with a mild (Becker) phenotype, that you need to investigate further?
• How does this analysis connect to your understanding of the genomic architecture of the DMD locus and the typical dosage alterations seen in these conditions?

How are you adapting to the situation?

• If your initial analysis yields ambiguous results, what alternative strategies are you considering? Could you review quality control (QC) metrics (e.g., probe ratios and standard deviations) or consider alternative analysis parameters?
• What support or guidance do you need right now? Do you need to seek immediate advice from a senior colleague on unusual patterns that deviate from expected findings or established guidelines?
• Are you ensuring that your interpretation remains within the scope of established laboratory protocols and your level of training?
• How are you ensuring your interpretation aligns with the clinical information provided in the referral and considers the potential implications for treatment options (e.g., eligibility for exon-skipping therapies)?

On action

What happened?

• How would you summarise the key aspects of the targeted genomic dosage analysis tasks completed for DMD/BMD?
• What were the referral reasons (diagnostic vs. carrier/familial) and which clinical details most influenced your interpretation?
• Which specific regions of the DMD gene did you analyse and what dosage changes (e.g. deletions or duplications) were observed?
• How did you identify unusual patterns, such as deviations from the reading frame rule, that required adjustments to your initial analysis?

How has this experience contributed to your developing practice?

• How did this activity improve your understanding of the genomic architecture of the DMD locus and associated large rearrangements?
• In what ways has this experience enhanced your ability to correlate genotype with phenotype (DMD vs. BMD) and evaluate eligibility for treatments like exon-skipping?
• How successful were you in determining carrier status in female relatives and resolving complex dosage patterns or technical artifacts?
• In what ways did your ‘reflection-in-action’ influence your final interpretation and contribute to a safe, high-quality service?

What will you take from the experience moving forward?

• Do you require further practice in identifying precise breakpoints or interpreting borderline results?
• What new strategies will you adopt for reviewing QC metrics or troubleshooting in future DMD cases?
• Which specific ‘next steps’—such as reviewing national guidelines or discussing clinical severity with senior colleagues—will you take to consolidate learning?
• What support or resources (e.g. databases or analysis platforms) have you identified as necessary for your ongoing development?

Beyond action

Have you revisited the experiences?

• Revisit your previous interpretations of DMD dosage results. Have any national recommendations for testing or reporting in DMD/BMD changed since you first completed this activity?
• Compare these experiences with other activities involving quantitative genomic data, such as copy number variant (CNV) analysis. What similarities or differences have you noticed in the analytical and interpretative processes?
• Review your reflections on this training activity alongside other paediatric genetic disorders. What broad learning points have emerged regarding the application of targeted genomic testing in paediatrics?
• Discuss challenging DMD cases or unexpected findings (such as non-conformance with the reading frame rule) with your peers or colleagues. Has their perspective offered new insights or alternative interpretations that you had not previously considered?

How have these experiences impacted upon your current practice?

• Recognise how your initial work with DMD/BMD has contributed to a broader understanding of gene dosage effects. How has this influenced your approach to interpreting results for other genetic conditions?
• How have you applied these dosage analysis skills in subsequent work or training? Have you become more confident in identifying potential pitfalls or technical limitations of these methodologies (e.g., MLPA or NGS-based dosage)?
• Consider how the learning from this activity supports your preparation for observed ‘in-person’ assessments, such as Case-based Discussions (CBD) or Observed Communication Events (OCE) involving complex paediatric findings.
• How might these contribute towards your future practice?
• Can you now more effectively explain the technical principles behind DMD dosage analysis and the clinical significance of different results to healthcare professional colleagues?
• What high-level skills—such as clinical reasoning, diagnostic planning, and technical troubleshooting—are you developing that will be vital in your future career?
• Identify clear next steps to stay current, such as keeping abreast of new technologies for dosage analysis or expanding your knowledge of rare dosage-related disorders.

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.