1. All Wales Molecular Genetics Laboratory
BRCA1 Presymptomatic testing:
Problematic case
Rhianedd Thompson - Cardiff
SCOBEC Training Day - Case Reports
15th Oct ‘08

2. All Wales Molecular Genetics Laboratory
BRCA1 Presymptomatic testing: Problematic case
Reason for referral: Predictive testing requested.
Information provided:
Family history of breast and ovarian cancer.
Mutation in family given as: BRCA1 2073insA (exon 11)
Proband name and a DNA reference number.
Letter from Barcelona lab about the familial mutation.

3. All Wales Molecular Genetics Laboratory
BRCA1 (Accession number U )

4. All Wales Molecular Genetics Laboratory
BRCA1 (Accession number U )

5. All Wales Molecular Genetics Laboratory
No mutation detected in the positive control.
Checked mutation numbering – appeared to be correct if using BRCA1 U reference sequence.
Checked accession number – not given in letter.
Checked which gene – clearly BRCA1 in the letter.
Checked proband’s name – not given in the letter.

6. All Wales Molecular Genetics Laboratory
Spoke to Barcelona.
Definitely BRCA1
Reference sequence confirmed: accession number U
Mutation numbering confirmed as that given in the letter.
Further information obtained = causes a premature stop in at codon 672
Proband’s name = Correct
Mutation isn’t there = Wrong DNA sample?

7. All Wales Molecular Genetics Laboratory
At what point did the sample mix-up occur?
Barcelona lab confirmed mutation was not present in their stored DNA sample.
Re-extracted from stored blood = mutation present.
Sample mix-up occurred after BRCA screening - familial mutation is genuine.
New sample sent to our lab = mutation present (HGVS = c.1961_1962dupA), predictive result reported.

8. All Wales Molecular Genetics Laboratory
This case highlights:
Need to obtain a copy of original report.
Difficulty in interpreting old mutation numbering systems.
Useful for future work to include the accession number of the reference sequence in report.
Need to keep a Spaniard in the lab.