Gemma Casebook Experience

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) 1992-99
• 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 - 1.5 pages long (lt 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-glucuronosyltra
  nsferase gene promoter Gilbert syndrome
• UGT1A1 genotyping in a Canadian Inuit population
• Gilbert syndrome is a contributory factor in the
  prolonged hyperbilirubinaemia of the newborn

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Cases (2, pre-CS)

• Localisation of a bile acid UDP-glucuronosyltransf
  erase 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 -gt PASS!

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Things to note

• 3 year deadline
• Using papers as cases can be more work than
  expected if papers cover lot of work

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(No Transcript)
11
PhD Option

• Investigation of the molecular basis of Spinal
  Muscular Atrophy (SMA) in South African Patients

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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

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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 -gtto identify 2nd mutation

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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

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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

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Initially...

• PhD thesis already completed
• Submitted an abstract to exams office to check
  suitability
• No response from college despite repeated emails
• ..........

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Then.....

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

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Update...

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