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Clinical classification of mutation R75Q
- Question
- Dear expert team,
the mutation R75Q (c.224G>A; p.Arg75Gön) was described as a sequence variation by Tussi et al. in 1992. Newer publications from about 2004 onwards speak of a variant that is associated with a CF-like phenotype, but they rule out the possibility that classic CF can be formed on the second allele in connection with a classic CF mutation. What are your experiences with carriers of this mutation?
Many thanks for your answer. - Answer
- Hello,
R75Q is not a CF mutation!
Whether R75Q is clinically relevant at all or whether it is only a polymorphism without clinical relevance is a highly controversial question. For example, an Italian working group reported that R75Q can be considered a genetic disposition for sarcoidosis (Bombieri et al., Eur J Hum Genet 2000; 8: 717 – 720.). In a German collective that was subsequently examined, this finding could not be verified: R75Q did not show any associations with sarcoidosis; in one family with R75Q it could even be shown that R75Q was not passed on with the disease (Schünemann et al., European Journal of Human Genetics (2002) 10, 729 – 732).
R75Q was also not found more frequently (but actually less frequently) in men who do not have spermatic ducts (so-called CBAVD) than in healthy controls (Dörk et al., Hum Genet (1997) 100 : 365–377).
All things considered, R75Q is at best a certain genetic modifier, i.e. the CFTR function could be affected to a small extent and would therefore have minor clinical effects. In most cases, R75Q is not a problem at all.
Kind regards
Prof. Manfred Stuhrmann-Spangenberg - 18.05.2012
