Rare Disease 2 —
Training activity: 5

Details

Review referrals; analyse, interpret and report the results of testing for Angelman syndrome referrals.

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 review referrals and perform targeted analysis for imprinting disorders?
• Contextualise the specific considerations:
• What fundamental knowledge do you need regarding genomic imprinting and the specific assays used, such as methylation-specific PCR (MS-PCR), MS-MLPA, or array CGH?
• Have you reviewed the diagnostic algorithms for AS and the national guidelines for reporting chromosomal abnormalities and imprinting defects?
• What technical metrics (e.g., methylation ratios, probe signal strength, or standard deviations) must you monitor to ensure a safe and high-quality service?

What do you anticipate you will learn from the experience?

• What insights do you hope to gain regarding the different genetic mechanisms leading to AS, such as maternal deletions of 15q11-q13, paternal uniparental disomy (UPD), imprinting centre defects, or UBE3A mutations?
• What do you already know about the parental origin of genetic material in this region and how it differentiates AS from Prader-Willi Syndrome?
• How do you anticipate this will improve your ability to interpret genomic variants and communicate their clinical implications to healthcare colleagues?

What actions will you take in preparation for the experience?

• Will you consult relevant literature on the genomic architecture of the 15q locus and established best practice guidelines for variant nomenclature?
• How will you gain clarity on laboratory-specific SOPs for AS testing?
• What potential difficulties do you anticipate, such as interpreting subtle methylation changes, identifying mosaicism, or managing results that are inconsistent with the clinical phenotype?
• How do you feel about embarking on this activity, given the significant diagnostic and prognostic implications for the patient?
• In what situations (e.g., an atypical methylation pattern or a variant of uncertain significance) will you seek immediate advice from a senior scientist to ensure you are working within your level of training and ability?

In action

What are you doing?

• How are you currently approaching the specific analytical steps for Angelman syndrome (AS)?
• Why is the data you are reviewing—such as methylation studies or copy number assays—specifically relevant to investigating imprinting disorders?
• What decisions are you making in the moment as you evaluate the data for abnormal imprinting, paternal UPD, or microdeletions in the chromosome 15 critical region?
• Which aspects of your practice feel intuitive, and which—such as ensuring the interpretation carefully considers parental origin—require more conscious effort?

How are you progressing with the activity?

• How effective are your current strategies in distinguishing between maternal deletions, paternal UPD, and imprinting centre defects?
• How are you managing real-time challenges like interpreting subtle methylation changes, identifying mosaicism, or differentiating between deletion subtypes?
• What are you learning about imprinting theory as the data unfolds, especially when encountering findings that do not fit neatly into expected patterns?
• In what ways do your current findings align with your understanding of imprinted genes within the 15q11-q13 region and the distinct clinical phenotype of AS?

How are you adapting to the situation?

• Which alternative or supplementary analyses, such as testing parental samples, are you considering for cases where it is difficult to differentiate between potential diagnoses?
• How are you identifying the point where you must seek immediate support or guidance from a senior colleague or imprinting specialist regarding a complex case?
• How are you ensuring that your real-time interpretation remains within your professional scope of practice and aligns with established laboratory protocols?
• How are you ensuring your interpretation accurately accounts for parental origin, given its critical importance for a definitive AS diagnosis?

On action

What did you notice?

• How would you summarise the key genomic data you analysed for suspected Angelman syndrome?
• Which specific assays (e.g., MS-PCR, MLPA, or array CGH) were involved in the investigation, and why were these chosen?
• What were the indicative findings (e.g., maternal microdeletion or paternal UPD) and did you observe any results that deviated from typical patterns?
• How did you feel while managing the technical and clinical complexity of this high-stakes diagnostic investigation?

What did you learn from the activity?

• How has your understanding of the diverse molecular mechanisms leading to AS (e.g., deletions, UPD, imprinting centre defects, or UBE3A mutations) developed through this activity?
• In what ways did you successfully resolve challenges, such as molecular results inconsistent with the clinical phenotype or difficulties distinguishing between epigenetic defects?
• How did your ‘reflection-in-action’ influence the final accuracy and technical quality of your interpretive report?
• How does mastering these complex imprinting interpretations relate to your future requirements as a Clinical Scientist in post-programme practice?

What will you take from the experience moving forward?

• What specific areas, such as the 15q critical region or the clinical nuances differentiating AS from PWS, require further study to deepen your understanding?
• How will you apply this learning to routine practice, specifically in being more attentive to methylation patterns or utilising new bioinformatic resources?
• Which specific ‘next steps’—including reviewing diagnostic algorithms, attending specialist seminars, or discussing cases with senior colleagues—will you take to consolidate your learning?
• What additional support or resources, such as specialist databases, expert mentorship, or updated reporting guidelines, have you identified as necessary for your ongoing development?

Beyond action

Have you revisited the experiences?

• How has your understanding of the complex molecular mechanisms underlying imprinting disorders evolved since your initial AS training?
• In what ways does comparing this activity with other epigenetic or parent-of-origin tasks deepen your comprehension of non-Mendelian inheritance patterns?
• What consistent themes or significantly deepened areas of testing strategy and interpretation have you identified through a review of your module reflections?
• How have discussions with clinical colleagues enhanced your understanding of the challenges in AS diagnosis and management?

How have these experiences impacted upon your current practice?

• In what ways are the clinical reasoning and technical troubleshooting skills developed here supporting your wider laboratory practice?
• How has your initial exposure to AS analysis shaped your current approach to other disorders involving epigenetic mechanisms?
• To what extent are you now more likely to consider imprinting as a potential explanation for unusual inheritance patterns encountered in routine work?
• How effectively are you applying this knowledge to multidisciplinary team (MDT) meetings or subsequent clinical discussions?
• How is this accumulated learning supporting your preparation for ‘in-person’ assessments such as CBDs, DOPS, or OCEs?

How might these contribute towards your future practice?

• How confidently can you now explain genetic/epigenetic AS mechanisms and the rationale for testing approaches to other healthcare professionals?
• Which high-level skills, such as diagnostic integration and reporting, do you recognise as vital for your future career as a Clinical Scientist?
• Which clear actions for continued development—such as staying updated on imprinting technologies or mastering complex methylation patterns—have you identified to ensure you remain at the forefront of the field?

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.