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BRCA1 mutation and neuronal migration defect: implications for chemoprevention
  1. D Eccles1,
  2. D Bunyan2,
  3. S Barker3,
  4. B Castle4
  1. 1Wessex Clinical Genetics Service, Princess Anne Hospital, Coxford Road, Southampton SO16 5YA, UK
  2. 2Wessex Regional Genetics Laboratory, Salisbury District Hospital, Odstock, Salisbury, UK
  3. 3Wessex Neurological Centre, Southampton General Hospital, Southampton, UK
  4. 4Wessex Clinical Genetics Service, Princess Anne Hospital, Southampton, UK
  1. Correspondence to:
 Professor Diana M Eccles MD FRCP
 Wessex Clinical Genetics Service, Princess Anne Hospital, Coxford Road, Southampton SO16 5YA, UK;

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Previously we described a BRCA1 carrier with a neuronal migration defect and postulated that the brain abnormality was caused by functional nullisomy for BRCA1.1 We now describe another family in which a similar type of neuronal migration defect has occurred in one of female identical twins with a BRCA1 gene mutation (MIM 113705). One twin developed unusually early onset multiple primary breast cancers while the second twin remains cancer free over a decade later. The second twin had long standing epilepsy and focal subcortical heterotopia. We hypothesise that the neuronal migration defect is due to focal nullisomy of the BRCA1 and that the modified breast cancer risk is due to the anti-oestrogenic effects of long term anticonvulsant therapy.

Thirty three year old identical twins were referred for genetic counselling. Twin 1 had developed breast cancer aged 29 years and a second primary breast cancer aged 33 years. The early onset of high grade oestrogen receptor negative breast cancer plus the family history (fig 1) suggested an inherited mutation in the BRCA1 gene.

Figure 1

 Family history. The early onset, high grade, oestrogen receptor negative breast cancer with multiple new primaries in the index case are typical for BRCA1. The young onset breast and ovarian cancer cases in immediate relatives in the previous generation are also typical.

Full mutation analysis on a DNA sample from twin 1 using the protein truncation test and denaturing high performance liquid chromatography failed to reveal any abnormality in BRCA1 or BRCA2. A set of 22 polymorphic markers spread across chromosomes …

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  • Competing interests: none declared