Startseite Medizin Double heterozygosity in the BRCA1 and BRCA2 genes in Italian family
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Double heterozygosity in the BRCA1 and BRCA2 genes in Italian family

  • Maria Teresa Vietri , Anna Maria Molinari , Gemma Caliendo , Maria Laura De Paola , D’Elia Giovanna , Anna Laura Gambardella , Pasquale Petronella und Michele Cioffi EMAIL logo
Veröffentlicht/Copyright: 12. August 2013
Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 51 Heft 12

Abstract

Background: Double heterozygosity (DH) is an extremely rare event in which both BRCA1 and BRCA2 are mutated simultaneously in a family. To date, few cases of DH have been reported, especially in Ashkenazi populations. In Italy some cases of DH have been reported. In this study, we have described an Italian family with double heterozygosity in the BRCA genes.

Methods: The proband is a 43-year-old woman with bilateral breast cancer. She presented two pathogenic mutations in both BRCA genes, IVS8+2T>A (c.547+2T>A;p.Gln148Aspfsx51) in BRCA1, K944X (c.2830A>T;p.Lys944X) in BRCA2 and a novel variant IVS4–57A>G (c.426–57A>G) in BRCA2, not previously described. Both mutations were inherited from the paternal lineage in the proband’s family. We investigated all available members of this family and we identified other two family members with DH.

Results and conclusions: Our observations support the hypothesis of a non-specific severe phenotype in DH carriers in terms of age of disease onset, cumulative lifetime risk and multiple primary tumours. Furthermore, our findings confirm that in order to identify all cases of DH, it is important not to limit the identification of mutations in a single gene, but extend the analysis to BRCA1 and BRCA2 and other breast cancer susceptibility genes.

Keywords: BRCA1/2 mutations; breast and ovarian cancer; double heterozygosity (DH)
Corresponding author: Prof. Michele Cioffi, Dipartimento di Biochimica, Biofisica e Patologia generale, Scuola di Medicina della Seconda Università degli studi di Napoli, Via L. De Crecchio 7, 80138 Naples, Italy, Phone: +39 81 5665680, Fax: +39 81 450169, E-mail:

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Received: 2013-04-08
Accepted: 2013-07-18
Published Online: 2013-08-12
Published in Print: 2013-12-01

©2013 by Walter de Gruyter Berlin Boston

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https://doi.org/10.1515/cclm-2013-0263
Schlagwörter für diesen Artikel
BRCA1/2 mutations; breast and ovarian cancer; double heterozygosity (DH)

Artikel in diesem Heft

  1. Letters to the Editor
  2. The addition of MESNA in vitro prolongs prothrombin time similar to N-acetyl cysteine
  3. Detection of unknown β-thalassemia cases from atypical HbA1c chromatograms
  4. Analytical study of a new turbidimetric assay for urinary neutrophil gelatinase-associated lipocalin (NGAL) determination
  5. The rare bipolar-contracted red cell significance and correlation with red cell volume
  6. Howell-Jolly body interference in reticulocyte counts
  7. PBMC expressed adiponectin mRNA is predictive of survival in patients with gastric cancer
  8. Comparison study of two commercially available methods for the determination of infliximab, adalimumab, etanercept and anti-drug antibody levels
  9. Development and validation of a rapid and reliable high-performance liquid chromatography method for methadone quantification in human plasma and saliva
  10. Reply to Ruiz-Argüello et al.: Comparison study of two commercially available methods for the determination of infliximab, adalimumab, etanercept and anti-drug antibody levels
  11. Still more discussion on the journal impact factor
  12. The order of draw, myth or science
  13. Masthead
  14. Masthead
  15. Editorial
  16. Multidisciplinarity and interdisciplinarity at work: the prenatal diagnosis
  17. Research Articles
  18. Prenatal diagnosis of inherited diseases: 20 years’ experience of an Italian Regional Reference Centre
  19. Prenatal diagnosis of haemoglobinopathies: our experience of 523 cases
  20. Prenatal diagnosis of cystic fibrosis: an experience of 181 cases
  21. Prenatal diagnosis of haemophilia: our experience of 44 cases
  22. Prenatal molecular diagnosis of inherited neuromuscular diseases: Duchenne/Becker muscular dystrophy, myotonic dystrophy type 1 and spinal muscular atrophy
  23. Editorials
  24. Journal impact factor: the debate continues
  25. Estimation of uncertainty in measurements in the clinical laboratory
  26. Review
  27. Searching for genes involved in hypertension development in special populations: children and pre-eclamptic women. Where are we standing now?
  28. Opinion Paper
  29. More discussion on journal impact factor
  30. General Clinical Chemistry and Laboratory Medicine
  31. Category-specific uncertainty modeling in clinical laboratory measurement processes
  32. The order of draw: myth or science?
  33. Planned variation in preanalytical conditions to evaluate biospecimen stability in the National Children’s Study (NCS)
  34. Longitudinal evaluation of thyroid autoimmunity and function in pregnant Korean women
  35. Evaluation of the N Latex free light chain assay in the diagnosis and monitoring of AL amyloidosis
  36. Identification of an important potential confound in CSF AD studies: aliquot volume
  37. Cancer Diagnostics
  38. Double heterozygosity in the BRCA1 and BRCA2 genes in Italian family
  39. Quantification of EGFR autoantibodies in the amplification phenomenon of HER2 in breast cancer
  40. Diabetes
  41. SAA1 genetic polymorphisms are associated with plasma glucose concentration in non-diabetic subjects
  42. Acknowledgment
  43. Acknowledgment
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