Cystic fibrosis (CF) is an autosomal recessive disease in which mutations in the CFTR gene cause various symptoms through its channel malfunction. Among over 1900 gene mutations, the most common mutation is ΔF508 which causes a trafficking defect of CFTR to plasma membrane (classified as ’class II‘ ). CF is quite rare in Japanese and listed in ’Intractable Diseases‘ by MHLW, Japan. Q98R mutation is the third most frequent disease associated mutation found in Japanese CF patients following H1085R and L441P. The Q98R mutation is in the class II same as H1085R, L441P and ΔF508 mutations.
Some pharmaceutical companies have been developing several expression correctors, e.g., lumacaftor, galicaftor, tezacaftor and elexacaftor, and channel function potentiators, e.g., ivacaftor, for ΔF508 mutation.
In this study we characterized the effects of the Q98R mutation on CFTR processing and investigated the effects of the Caucasian CF drugs on the expressions and functions of Q98R-CFTR.
From our in vitro data, it is suggested that Orkambi, a combination of lumacaftor and ivacaftor, is a potential candidate in the pharmaceutical therapy for Japanese CF patients with the Q98R CFTR mutation.