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Mutation Class Assignment for Q493R

Question
My daughter carries the delta508 and a rare Q493R. Can you please help me understand the mechanical defect of this protein caused by this sequence variation Q493R. My best guess from literature is that it is Class III (defective channel regulation). Thank you!
Answer
Thankyou for your question. There is not a great deal known about the Q493R mutation. This particular missense mutation was identified in a Bulgarian CF subject in 1994. Missense mutations are indeed often class 3 mutations, however they do not exclusively fall into this group. Furthermore, the classes of mutation themselves are not mutually exclusive.[1] At present, it is not entirely clear which class that Q493R predominantly resides. Our current understanding is that Q493R tends to confer a moderate to severe CF phenotype.[2]
The future is promising for CF subjects who have class 3 mutations. New therapies have been developed which serve to reduce the burden of disease in those CF subjects with the more common of these mutations.[3] It is hoped and anticipated that the beneficial effects of these new drugs will also pertain not only to the more rarer class III mutations, but also class 2 and 4 mutations.[4]

References
1. Rowntree, R.K. and A. Harris, The phenotypic consequences of CFTR mutations. Ann Hum Genet, 2003. 67(Pt 5): p. 471-85.
2. www.genet.sickkids.on.ca/MutationDetailPage.external?sp=239

3. Ramsey, B.W., et al., A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med, 2011. 365(18): p. 1663-72.

4. Elborn, J.S., Fixing cystic fibrosis CFTR with correctors and potentiators. Off to a good start. Thorax, 2011.
12.01.2012