Clinical expression of cystic fibrosis in a large cohort of Italian siblings (original) (raw)
Related papers
Genetic characterization of cystic fibrosis patients in Portugal
European Respiratory Journal, 2013
Objective: The aim of the study is to estimate the frequency of p.F508del and of the more common mutations in population of patients with cystic fibrosis (CF) followed at CF centers in Portugal, before the implementation of a pilot program of neonatal screening (NBS). Method: collection of data from the data bases of all the cystic fibrosis centers in Portugal. Patients in follow-up during 2012 were included, age was considered as for the 31st December. Results: 298 patients (pts) were identified: 140 (47%) males, 158 (53%) females, 5 with less than 1 year (y), 8 aged 1-2 y, 24 aged 3-5 y, 63 aged 6-10 y, 76 aged 11-17 y, 80 aged 18-29 y, 28 aged 30-39 y and 14 older than 40 y. p.F508del mutation is the commonest one: 143 pts (48%) homozygous and 92(30.8%) heterozygous. The 10 more common mutations found are F508del (63.4% of the alleles), R334W (5%), A561E (2.9%), G542X (2.7%), N1303K (2.2%), G85E (1.8%), R1066C and 3272/26A-G (1.3% each), Q1100P (0.8%) and P2055 (0.7%). Ten mutati...
Journal of Cystic Fibrosis, 2006
We report an example of atypical CF, i.e., a family in which three siblings were affected by late-diagnosed mild CF, and showed discordant pulmonary and pancreatic phenotypes. Sibling no. 1 (male), showed a severe pulmonary involvement and pancreatic sufficiency; sibling no. 2 (female) showed a mild pulmonary disease with pancreatic sufficiency; sibling no. 3 (male) had a very mild pulmonary expression and pancreatic insufficiency. The sweat test was altered in all three siblings, and all had intestinal occlusion in young age. The whole scanning of CFTR revealed the rare F508del/D614G genotype. The discordance of clinical expression within the same family reinforces the putative role of modifier genes of CF phenotype.
Cystic Fibrosis: Correlations between Genotype and Phenotype
Journal of Clinical & Cellular Immunology, 2015
Cystic fibrosis is a clinical entity with multiple representations. Despite acquired knowledge, there is still unknown information about this disease. We tried to define the relationship between classes of mutations and clinical manifestations. We also tried to structure clinical manifestations depending on the most commonly found mutations, not minimizing intervention of environmental factors and modifier genes. We found that patients from the same family with the same mutation had different clinical manifestations, thus highlighting intervention of environmental factors and modifier genes. Diagnosis of cystic fibrosis is not easy because there are sometimes symptoms blurred, sometimes suggestive, but support the diagnosis by laboratory methods is not always possible. It is important that this condition be diagnosed as early as possible, even at birth, in order to prevent complications of the disease.
Genotype-phenotype relationship in 12 patients carrying cystic fibrosis mutation R334W
Journal of Medical Genetics, 1997
We present a phenotype-genotype correlation analysis in 12 patients with cystic fibrosis (CF) carrying the mutation R334W in the CFTR gene. The clinical data obtained for this group were compared with the clinical data of AF508/ AF508 patients. Current age and age at diagnosis were significantly higher in the R334W mutation group (p=0.028 and p=0.0001). We found a lower rate of Pseudomonas aeruginosa colonisation in patients carrying the R334W mutation, although the difference was not found to be statistically significant. However, we found a statistically significant higher age of onset of Pseudomonas aeruginosa colonisation (p=0.0036) in the group of patients with the R334W mutation. Thirty three percent of R334W patients were pancreatic insufficient, significantly lower than the AF508/AF508 patients (p=0.004). We also found that the weight expressed as a percentage of ideal weight for height was significantly higher in patients with the R334W mutation (p=0.0028).
Clinical features of cystic fibrosis patients with rare genotypes
Journal of Medical Genetics, 1996
We describe the clinical features of seven cystic fibrosis patients from southern Italy who bear rare genotypes: (1) a patient homozygous for the 2183 AA-8G mutation who was affected by a very early pulmonary form of cystic fibrosis, and five patients who were compound heterozygotes either for the 2183 AA-+G mutation or for the I148T mutation, in both instances with the AF508 mutation; and (2) a patient homozygous for the early nonsense R553X mutation who showed only a moderately severe form of cystic fibrosis. Our results confirm that environmental or genetic factors unrelated to the CF disease contribute significandy to the development of the phenotype. (JMed Genet 1996;33:73-76) 1996 33: 73-76 J Med Genet G Castaldo, E Rippa, V Raia, et al. with rare genotypes. Clinical features of cystic fibrosis patients http://jmg.bmj.com/content/33/1/73
The influence of genetics on cystic fibrosis phenotypes
Cold Spring Harbor perspectives in medicine, 2012
Technological advances in genetics have made feasible and affordable large studies to identify genetic variants that cause or modify a trait. Genetic studies have been carried out to assess variants in candidate genes, as well as polymorphisms throughout the genome, for their associations with heritable clinical outcomes of cystic fibrosis (CF), such as lung disease, meconium ileus, and CF-related diabetes. The candidate gene approach has identified some predicted relationships, while genome-wide surveys have identified several genes that would not have been obvious disease-modifying candidates, such as a methionine sulfoxide transferase gene that influences intestinal obstruction, or a region on chromosome 11 proximate to genes encoding a transcription factor and an apoptosis controller that associates with lung function. These unforeseen associations thus provide novel insight into disease pathophysiology, as well as suggesting new therapeutic strategies for CF.