The importance of penetrance

2.24 ‘Penetrance’ is the term used to describe the degree of likelihood (based on clinical studies) that an individual carrying a particular genetic trait that could cause a disorder will actually develop it.[22] This can vary from very low to very high. For instance, it is possible to speak of the penetrance of each particular mutation (or combination of mutations) causing cystic fibrosis (CF). For the mutation known as ‘DF508’, the penetrance is high—about 99%. For other alleles, the penetrance is lower—but this calculation is also dependent upon the definition of the disease.[23]

2.25 Mutation in the so-called ‘breast cancer gene’, BRCA1, which is found in up to 1% of women in certain populations, is another example. Its presence is said to increase the risk of developing breast cancer by a factor of five. However, only 60–85% of women with a BRCA1 mutation will develop breast cancer during their lifetimes (that is, 60–85% penetrance). In other words, 15–40% will not do so.

2.26 HD is an example of a condition with a very high penetrance, approaching 100%. Those who test positive for the HD mutation will almost always develop the disease if they live long enough.[24] However, even for HD, some people may develop the disease very late in life, or die of something else before they manifest symptoms.[25]

2.27 Table 2–1 contains further information about penetrance for a range of medical conditions. However, the figures must be read in context. As discussed above, the penetrance and severity of genetic disorders may not be the same for all persons.

[22] R Trent, Molecular Medicine: An Introductory Text (2nd ed, 1997) Churchill Livingstone, 47.

[23] In the case of cystic fibrosis, for example, clinicians must consider whether male infertility in the absence of any other clinical signs is a ‘condition’, a ‘disease’, or nothing of significance.

[24] R Trent, Molecular Medicine: An Introductory Text (2nd ed, 1997) Churchill Livingstone, 58. See also M Ridley, Genome: The Autobiography of a Species in 23 Chapters (1999) Fourth Estate, London, 55‑66.

[25] There is on-going research to determine the extent to which an enriched environment (mental stimulation, physical activity etc) may delay the onset of HD and other degenerative diseases. See A van Dellen and others, ‘Environmental Effects on Huntington’s Disease in Transgenic Mice’ (2000) 404 Nature 721, 721–722, discussed on the ABC Radio program ‘The Science Show’, 15 April 2000: The Science Show, Huntington’s Disease Study, Radio National, <>, 19 February 2003.