A citation taken from an article discussing 12 cases of those with the R334W mutation (most of whom also had the DF508 mutation.) Full article can be found here: <a target=_blank class=ftalternatingbarlinklarge href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1050858/pdf/jmedgene00244-0001.pdf">Genotype-phenotype relationship in 12 patients carrying cystic fibrosis mutation R334W</a><br><br><div class="FTQUOTE"><begin quote>The R334W mutation of the CFTR gene is a<br>missense mutation, first identified in 1,991,'<br>that corresponds to the substitution of an<br>arginine by a tryptophan at position 334 in<br>exon 7 of the CFTR gene. R334W is a class IV<br>(defective conductance) mutation.'2 Class IV<br>mutations (for example, RI 17H, R334W, and<br>R347P) occur in the membrane spanning<br>domains and are predicted to cause a mild CF<br>phenotype.'2<br><br>The R334W mutation has been described in<br>a number of patients in different populations,<br>although the worldwide prevalence is less than<br>0.1 %. In our CF patients, R334W has a prevalence<br>of 4.9% (10/204 CF chromosomes). The<br>association of intragenic microsatellite haplotypes<br>17-46-13 (IVS8CA-IVS17BTAIVS17BCA)<br>with the different R334W chromosomes<br>points to a single origin in the<br>Spanish families described previously."<br><br>Our results provide new data to support that<br>patients with the R334W mutation suffer less<br>severe expression of the disease and that the<br>disease can be diagnosed later, as reported by<br>Estivill et al.'4 The proportion of pancreatic<br>insufficient patients with the R334W mutation<br>in our study is lower (33%) when compared to<br>the proportion of pancreatic insufficient patients<br>in the paper by Estivill et al'4 (60%). In<br>our study the number of pancreatic sufficient<br>patients with R334W varied according to the<br>age at which pancreatic status was assessed, the<br>later the age the smaller the number of pancreatic<br>sufficient patients, with most patients being<br>pancreatic sufficient at 20 years of age. It may<br>suggest that pancreatic function in this group<br>of patients declines with age. This fact is<br>supported by the pancreatic status found in<br>patients 10, 11, and 12, belonging to the same<br>family. While patients 10 and 12 are at the<br>lower limit of pancreatic sufficiency, patient 11<br>has minimal pancreatic insufficiency.<br><br>Chronic infection with PA is the main cause<br>of morbidity and mortality in CF patients. We<br>did not find statistically significant differences<br>with regard to lung colonisation by this pathogenic<br>bacteria, although a lower rate of colonisation<br>was found in R334W patients. A slightly<br>higher proportion of lung colonisation in<br>R334W patients compared to AF508/AF508<br>patients has previously been reported,14 although<br>the lung colonisation was referred to as<br>bacterial pathogens in that report. On the other <br>hand, a significant higher age at colonisation<br>was found in our group of patients suggesting<br>that R334W may be a lower risk allele than<br>AF508 for the acquisition of PA.<br><br>Interfamilial and intrafamilial clinical diversity<br>for pancreatic insufficiency and the variation<br>in pulmonary disease indicates that other<br>factors, either genetic or environmental, must<br>affect the severity and progression of the<br>disease. In fact, it has been recently shown that<br>the severity of CF in mice can be modified by<br>at least one unlinked genetic locus."5 Environmental<br>factors, such as age at diagnosis, a previous<br>affected sib, medical care, or degree of<br>compliance with treatment regimens, may further<br>contribute to the variatiation of the clinical<br>spectrum of the disease in CF patients.</end quote></div><br>
