1. Gemma Casebook Experience
Background
PhD & postdoctoral research (7 years)
Clinical scientist 1997
FRCPath Part 1 exam 2000
Started thinking about options 2002
First considered PhD option
relevant but too old (1994)
Next considered Papers option
6 first author papers (pre-CS) –
Relevant (some too old)

2. Decision - Casebook Each of 6 (pre-CS) papers as individual cases
Updating content & discussion
7th case - paper reviewing an immunodeficiency service (work carried out as CS)
8th case – interesting Wiskott-Aldrich syndrome family (work carried out as CS)

3. Casebook Proposal Submitted proposal in 2003
Short & simple pages long (< 1hr)
Stated that data from 7 papers presented & discussed in light of recent findings
Then listed 7 cases by their paper titles
Stated 8th case would cover an interesting immunodeficiency family
News proposal approved within few months

4. Casebook Title
“Molecular Analysis of the UGT1A1 TATA Box in a Gene Family Associated with Crigler-Najjar and Gilbert Syndrome and Genes associated with Wiskott-Aldrich and Hyper IGM Syndromes”

5. Cases (pre-CS)
Genetic variation in bilirubin UDP- glucuronosyltransferase gene promoter & Gilbert syndrome
UGT1A1 genotyping in a Canadian Inuit population
Gilbert syndrome is a contributory factor in the prolonged hyperbilirubinaemia of the newborn

6. Cases (2, pre-CS)
Localisation of a bile acid UDP- glucuronosyltransferase gene (UGT2B4) to chromosome 4 using PCR
Isolation of a human YAC contig encompassing a cluster of UGT2 genes & its regional localisation to chromosome 4q13
Structure of the human UGT2B4 gene encoding a bile acid UDP- glucuronosyltransferase

7. Cases (3, work as CS)
Use of X-inactivation analysis to infer carrier status in a family with Wiskott- Aldrich syndrome
Review of the screening service for Hyper IgM at GOSH

8. Writing Casebook The first 6 cases – mostly done by mid 2005
1 year maternity leave, returning mid 2006
Unaware - must submit within 3 yrs of proposal accepted!!
Now 3.5 years later
Spoke to RCPath – allow 4 yr to submit (due to 1yr maternity)
Submitted at 4 yrs – 3-4 months -> PASS!

9. Things to note 3 year deadline
Using papers as cases can be more work than expected if papers cover lot of work

11. PhD Option
“Investigation of the molecular basis of Spinal Muscular Atrophy (SMA) in South African Patients”

12. Introduction & Aim Pilot SMA study in S Africa
65% black SMA patients homozygous SMNt gene del (95% in white)
Different molecular basis of SMA in population
Aim to investigate molecular basis of SMA in SA black population

13. Methods & Results Dosage assay for SMNt del heterozygotes developed
Heterozygosity confirmed in 70% “non- homozygous del” black SMA patients
Carrier frequencies determined for black & white SA populations
SSCP, seq & blot ->to identify 2nd mutation

14. Methods & Results (2) 3 seq variants, none functionally significant
Blot –no large scale rearrangements
Linked marker analysis (8 linked markers)
No common chromosomal background for 2nd mutation

15. Conclusions SMA in South Africa more common than previously thought
Inclusion of SMNt dosage assay into service increases % of cases in which diagnosis can be confirmed
Allow carrier detection
Thought that a rearrangement of SMNt gene in black SMA population - unconfirmed

16. Initially... PhD thesis already completed
Submitted an abstract to exams office to check suitability
No response from college despite repeated s

17. Then..... Submitted covering letter 1 copy of thesis
Confirmation of award of the degree CV
Update on new developments since thesis written (2003)

18. Update... Disease / population specific updates Technical Advancements
No further work had been carried out
Technical Advancements
MLPA for dosage
Technique explained & eg results given