Portfolio interview Flashcards
What are the good scientific practice domains?
- Professional practice
- Scientific practice
- Clinical practice
- Research, development and innovation
- Clinical leadership
Describe the NHS constitution
- The NHS provides a comprehensive service, available to all
- Access is based on clinical need, not ability to pay
- Aspires to the highest standards of excellence and professionalism
- The patient is at the heart of everything we do
- Work across organisational boundaries eg local authority, public, private and voluntary organisations
- Best value for money
- Accountable to the public, communities and patients it serves
What are the NHS values?
- Working together for patients
- Respect and dignity
- Commitment to quality care
- Compassion
- Improving lives
- Everyone counts
Describe CML and its clinical presentation.
CML, chronic myeloid leukaemia:
Myeloproliferative neoplasm originating from pluripotent stem cells - granulocytes are the main component
Usually developes slowly, presents with mild symptoms such as fatigue, night sweats, weight loss, anaemia and bone pain. ~50% are asymptomatic and are discovered by high wbc count observed on a routine blood test.
Commonly occurs around 60y/o but can occur in any age. 15% of leukaemiaswith slight male predisposition.
Characterised by a reciprocal translocation between chromosomes 9 and 22.
t(9;22)(q34.1;q11.2) - Philadelphia chromosome in 95% BCR-ABL1. 5% may have variant or cryptic translocation.
Describe ALL
ALL, acute lymphoblastic leukaemia.
Second most common leukaemia in adults. Malignant transformation of lymphoid progenitor cells in bone marrow. >20% blasts in BM or blood.
80% occur in children. 75% of adult all is B-ALL, 25% T-ALL
Etv6-runx1 - common in children
Describe QF-PCR and its use in prenatal testing
Screening of aneuploidy for T13/18/21 and XY sex abnormalities
Preformed on CVS/Amnio
Uses highly polymorphic STRs that are identifiable using fluorescent labelled primers.
What is CPM ( confined placental mosaicism)
The presence of chromosomal abnormalities in the extra-embryonic tissue, which are absent from the fetal tissue.
How does CPM arise
Mitotic CPM - trisomic cell line arises from postzygotic mitotic duplucation of one chromosome in the progenitors of a placental cell lineage eg trophoblast.
Meiotic CPM - trisomic zygote is rescued at the blastocyst developmental stage by loss of the extra chromosome during mitotic cell division in the embryonic progenitor cells (while progenitors in the placenta remain trisomic). May be associated with UPD - thoerically 1/3 should show UPD. May affect in uterine growth.
What would you do to rule out cpm or mosaicism suspected on QF-PCR
FISH on short term and long term cultures - according to European guidelines ‘where cpm is likely cause of discrepant result, ultrasound monitoring should be recommended on the report’
What is MS-MLPA and what are its uses
Methylation specific ligation dependant probe amplification;
Variant of standard MLPA which combines copy number repeat with methylation sensitive restriction enzyme (HhaI) to produce a semi-quantitative interpretation.
Enables the detection of imprinting pattern in PWS or Angelman, beckwith-Wiedemann/Russel silver syndrome.
Clinical features of Prader-Willi
Hearing loss Developmental delay - particularly language Excessive eating, raised bmi Hypotonia (floppy) Shorter stature
Describe sensitivity and specificity
Sensitivity; the ability of a test to correctly identify patients with a disease.
Sensitivity = true positives ÷ (true positives + false negatives)
Specificity; the ability of a test to correctly identify patients without a disease
Specificity = true negatives ÷ ( the negatives + false positives)
Describe an Autosomal Dominant disorder ( Huntington Disease)
Progressive degeneration of nerve cells in brain = tremors, seizures and contraction of muscles. Progressive disease.
CAG trinucleotide repeat in the HTT gene. 10-35x = normal. 36-120+ = production of abnormally long Huntingtin protein which is cut up by the cell to produce smaller fragments which aberrantly bind to neurons impairing function.
CAG repeat displays anticipation through generations.
Presents in 30-40 y/o
Define validation and verification
Validation = are we doing the correct test
Verification = are we doing the test correctly
Describe an autosomal recessive disease (Cystic fibrosis)
Carrier frequency 1/22 in mid Trent region.
Usually characterised by airflow limitations with recurrent infections and nutritional deficiency due to exocrine pancreatic impairment. Male infertility due to congenital absence of vans deferens or bilateral ejaculatory duct obstruction.
CFTR chromosome 7. Mutations effect the transport of chloride across membrane. Delta F508 80% in Trent region.
Newborns = failure to produce first bowl movement (meconium ileus). Failure to thrive, infections.
What are the different types of CF mutation?
Class 1: no functional CFTR created (22% of CF with at least one mut)
Class 2: CFTR protein is created but misfolds, keeping it from moving to cell surface. (eg DeltaF508) (88% of CF with at least one mut)
Class 3: CFTR protein is created And moves to cell surface but channel gate doesn’t open (6%)
Class 4: CFTR protein is created and moves to cell surface but channel is faulty.
Class 5: normal CFTR protein is created and moves to the cell surface but in insufficient quantities.
What is the purpose of Poly T analysis for CF and in which cases would you test
Can function as a CFTR mutation in some CF related cases and can effect the severity of other mutations (R117H). Should not be performed routinely in the context of carrier testing relatives, partners of carriers/patients, or echogenic bowel referrals.
Performed on:
1. Obstructive azoospermia cases
2. Diagnostic CF referrals with R117H
3. Bronchiectasis or pancreatitis cases with one mutation detected
4. Testing clinically requested, such as general male infertility
What might cause a false negative result on CF kit testing
Mutation not covered by kit
Variant within the primer binding site
