What percentage of people fall into the gray area?
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Q. What percentage of people tested fall into the ‘gray area?' either with reduced penetrance or intermediate? Is it very common? Thank you?
Sarah, Young adult
A. Dear Sarah,
Many thanks for your question. The percentage of people with a CAG size in the ‘gray area’ is thought to be low, although research has been a little limited with regards the exact frequency of intermediate/reduced penetrance alleles. A recent study found that 5.8% of people (without a family history of HD) carry an intermediate allele (IA). This study was based in Canada, so in other populations the percentage may be different, and in our experience the number of people with an IA seems lower than this. The frequency of reduced penetrance (RP) alleles also appears to be quite low, but again exact figures are quite hard to come by.
As you may know, there is evidence that CAG repeat sizes in the gray area tend to be more unstable when passed from one generation to the next, although even in this range the CAG repeat size usually stays the same. It is still unclear as to exactly how often an IA/RP would expand into the full HD range, and hopefully further research will help clarify this in the coming years.
When we are discussing predictive genetic testing for HD in our clinic, we always include information about the possibility of IA/RPs, but usually when there is a family history of HD we expect a clear cut result (i.e. a result of fewer than 27 or more than 39 CAG repeats).
I hope this is helpful, and please do not hesitate to get back to us if you have any further queries