Age-dependent penetrance of different germline mutations in the BRCA1 gene

Fahd Al-Mulla, J. M. Bland, D. Serratt, J. Miller, C. Chu, G. T. Taylor

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)


Aims: BRCA1 gene mutations have been extensively studied in relation to breast and ovarian cancer susceptibility. Various genotype-phenotype correlation attempts have yielded important data pertaining to the consequences of BRCA7 mutations. However, little is known about the effects of recurrent BRCA mutations on expressivity and the age of onset of cancer in a population. This study addresses whether different exon mutations have variable expressivity especially in relation to the age of onset of breast cancer. Methods: Using a step-wise systematic approach, culminating in the sequencing of all BRCA7 and BRCA2 exons with the addition of multiplex ligation-dependent probe amplification, the relationship between disease phenotypes and gene mutations in 219 individuals and their family members was examined. Results: It is shown that different BRCA7 gene mutations have distinct effects that influence the age of onset of breast or ovarian cancer. Mutations in exon 2 of the BRCA7 gene had significantly lower penetrance compared with mutations of exons 11, 13 and 20. The median age of affliction with breast cancer was 55 years for 185delAG in exon 2 (95% confidence interval (CI) 46.7 to 59.5), 47 years for the 4184delTCAA mutation in exon 11 (95% CI 39 to 55.4), and 41 years for exon 13 duplication (95% CI 32.9 to 49.7) of the BRCA7 gene. Moreover, 14 novel mutations in BRCA7 and BRCA2 genes in the Yorkshire/Humberside population were identified. Conclusions: The 185delAG mutation of the BRCA7 gene is a low penetrance mutation that is age dependent especially when compared with the exon 13 duplication mutation. The data have important ramifications on screening, genetic counselling and prophylactic treatment of BRCA1 gene mutation carriers..

Original languageEnglish
Pages (from-to)350-356
Number of pages7
JournalJournal of Clinical Pathology
Issue number4
Publication statusPublished - 1 Apr 2009


Dive into the research topics of 'Age-dependent penetrance of different germline mutations in the BRCA1 gene'. Together they form a unique fingerprint.

Cite this