Problem Solving (clinical scientist)

Question 1

How would you deal with an incidental finding?

Answer 1

• We would report an incidental finding if results are clearly pathogenic
• A principal clinical scientist would call clinician to see if they would understand / be able to deliver the results
• Example with Lynch finding
• If clinician was not familiar- report to include that the patient and their family are highly recommended to be referred to clinical genetics.

Any findings of uncertain significance would not be reported.

Any findings in prenatal array would need to be considered carefully - due to potential for TOP based on findings

Question 2

What would you do if you suspected a potential sample mix up (Molecular)

Answer 2

Mix up can have extensive implications and risk of reporting incorrect results
• Could involve multiple patients and could result in the reporting of incorrect but plausible results
• Multiple procedures in place to minimise risk (transfer checks and label checks)
• Alert principal scientist initially (in case any results need to be recalled /embargoed)
• Try to determine if mix up is genuine
• Any information on referral / paperwork / SCR
• Has patient had a BMT
• Consider possibilities that could result in anomalous result
o SNP under primer binding site
o Deletion within that region
o Non-paternity
o Adoption
o UPD

• Gather information about booking in process, DNA extraction, PCR loading, checks – to see if anything abnormal / unusual is present

Question 3

What if you identify that a sample mix up is suspected after you have investigated?

Answer 3

• If sample mix is suspected – alert line manager to help with investigation
• Alert all individuals with samples / patients on that run – place embargo on all samples “DO NOT REPORT, POTENTIAL MIX UP”
• Repeat testing using controls
• STR analysis with DNA and DNA extracted from blood spot
• If no mix up- remove embargo and report
• If mix up confirmed – identify where it has occurred
• Highlight this in comments for sample
• Perform root cause analysis (head of section) and liaise with local incident manager
• Discuss at CIG
• Lost sample
• There is an SOP for lost samples
• Need to check all surrounding areas
• Check all areas within the laboratory where sample has been

Question 4

How would you deal with sex mismatch on array?

Answer 4

• Rule out any possible mistakes that may have been made
o Check patient records on database and check sex on all paperwork
o Get SCR search to determine sex
o Rule out the possibility that patient has had BMT
o Check all tubes are in the correct place
• If there is no explanation
• Possible contamination
• Inform relative hubs, clinical scientsts, senior scientists
• Ask hub to check:
o extraction worksheet (anything unusual)
o Check blood tubes labelling etc
o Request a repeat extraction
o Extract from blood spot
o Perform ID check using markers between DNA from blood spot and DNA extracted
o Ensure no patients are reported that were on that extraction worksheet until this has been resolved
• If no clear reason – request repeat sample

Question 5

Describe the importance of error logging

Answer 5

• Error logging enables us to identify patterns in errors / frequency / severity in errors
• Enables errors to be investigated in depth using root cause analysis
• Determine why and how the error has happened
• Usually, errors indicate a weakness in a system or process
• Error logging enables us to identify weaknesses and improve systems to prevent errors from reoccurring
• Ultimately forms a part of clinical governance - and enables us to improve overall patient care

Question 6

Describe a time when you have made a mistake

Answer 6

o I had written a Presymptomatic report for a patient with a family history of arrhyhtmogenic right ventricular cardiomyopathy, which was signed out.
o I later noticed that I had wrongly described the family history of the patient as dilated cardiomyopathy when it should have been arrhythmogenic right ventricular cardiomyopathy.
o I understood that this could cause confusion for both the clinician reading the report and anyone else who might read the report.
o I immediately notified my line manager and requested that we issue an updated report
o I then informed the clinician so tht they were aware of the typo
o They assured me that this had not had any negative consequences
o In order to try and prevent typos like this, I now try to leave some time between writing a report and handing it in for reporting so that I can proof-read in order to try and avoid these types of errors in future.

Question 7

How would you deal with a confirmation test that has come back as normal?

Answer 7

*Confirmation testing always uses positive controls to ensure assay is working.

• If result was normal, we would always repeat using positive controls a confirmation initially as this is considered to be unexpected
• If it comes back as normal again, determine whether there may be any reason to suspect this may not be real result
• Cancer - high probability of phenocopies

*Could also consider possibility of SNP under primer binding site, deletion, UPD, Familial relationship not confirmed

• Depending on test - we would either report saying their features are not likely to be due to familial variant and explain limitations of testing
• We say to contact lab for further info, so if strong suspicion still present, we could acquire repeat sample and repeat testing again.

*If carrier test (obligate carrier) come back as normal, we might investigate further. Identity testing (with permission)

Question 8

Possible reasons that could cause discrepant result

Answer 8

• Sample mix up
• Non paternity
• Adopted
• Parentla Germline Mosacisism
• Gene conversion
• SNP under primer
• Bone marrow transplant

Question 9

Describe a case where you had to use problem solving?

Answer 9

*MLPA Apparent duplication

• Performed Lynch screen
• Identified apparent MLH1 dup
• Asked for repeat sample
• Repeat sample - no dup detected
• Repeated again using 2 different MLPA kits (same results)
• recorded all data and results on sep. document
• Identified a third sample for patient, so tested this
• Results still same
• Considerations for sample mix up
• Performed ID testing between all 3 - they were the same patient.
• Consider technical reasons
• Contacted lab and asked about:
• DNA extractions
• Sample type
• Patient on any treatment?
• Any IHC results
• Blood stored at 4 deg. 4 months
• MRC Holland
• Biassed DNA extraction

*Issued new report outlining this and wrote report as negative report and explained dup was artefact.