Phenotypic discordance in three siblings affected by atypical cystic fibrosis with the F508del/D614G genotype (original) (raw)
Related papers
Journal of Medical Genetics, 1996
To study the severity of mutation G85E, located in the first membrane spanning domain of the CFTR gene, we studied the clinical features of 13 Spanish patients with cystic fibrosis (CF) carrying this mutation. G85E accounts for about 1% of Spanish CF alleles. One patient was homozygous G85E/G85E and the rest were compound heterozygotes for G85E and other mutations (AF508 nine patients, A1507 two patients, and 712-1G>T one patient). The characteristics of the pooled G85E/any mutation group were compared with those of 30 AF508 homozygotes. Mean age at diagnosis and percentage of ideal height for age were higher in the G85E/any mutation group (4.2 (SD 4.7) v 2.4 (SD 2.3), p<0.05, and 102.8 (SD 4.7) v 97.8 (SD 4.1), p<0.01)), both probably related to the greater prevalence of pancreatic sufficiency (70% v 0%, p<0O01). The G85E homozygote was pancreatic sufficient. Sweat sodium levels were slighdy higher, and salt loss related problems more frequent, in the G85E/any group. Two of the G85E patients died of respiratory failure aged 6 and 14 years. Striking discordance in the phenotype was observed in two pairs of sibs, one of them dizygotic twins, suggesting that factors, genetic and environmental, other than CFTR genotype are important in determining CF phenotype.
Genetics of cystic fibrosis: Basics
Archives de Pédiatrie, 2020
Cystic fibrosis (CF) is an autosomal recessive genetic disorder whose responsible gene-the CFTR gene-was discovered 30 years ago by a positional cloning strategy. This gene, which encodes a chloride channel, contains more than 2,000 mutations including a major one (p.Phe508del). This discovery has led to considerable progress in the understanding of the pathophysiology of CF as well as in the management of patients and their families. It has also paved the way for the development of specific therapies for the disease. From an epidemiological point of view, the incidence of CF, which shows loco-regional variations, is now estimated at 1/4,700 live births in France. The face of CF has dramatically changed over the past decades: CF has gradually become a disease of the adult with, today, more than 50% of the patients being 18 years old or more and a median predicted survival age that exceeds 45 years.
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.
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.
CFTR gene analysis in patient with atypical cystic fibrosis
Jugoslovenska medicinska biohemija, 2004
This paper reports a case of a patient presenting with atypical cystic fibrosis whose sweat test shows borderline values. In vast majority of cases the sweat test is essential diagnostic tool for establishing the diagnosis of cystic fibrosis, but only after the molecular genetic testing the diagnosis can be confirmed. The patient was found to be compound heterozygote for two CFTR mutations, F508del and D1152H. The presence of F508del mutation was analyzed by PSM method, while the screening for the second mutation was performed using DGGE. The strategy of mutation detection in cystic fibrosis patients, especially those with atypical presentations who carry less frequent mutations, should include both direct and indirect methods of molecular diagnostics.
American Journal of Medical Genetics, 1995
We describe patients inheriting cystic fibrosis (CF) mutation 3849+10kb>T as homozygotes or compound heterozygotes. Three unrelated homozygotes for this mutation were all pancreatic-sufficient and sweat testnegative or inconclusive. Among the compound heterozygotes, both pancreatic sufficiency and insufficiency, as well as positive and negativehnconclusive sweat test results are reported, expanding the range of clinical expression associated with inheritance of this mutation. 3849+lOkbC>T is one of several CF mutations that can result in atypical or variant forms of CF. For geneticists, the diagnosis of variant CF has implications for recurrence risk and prognosis counseling of the families of affected individuals, and possibly for CF carrier screening in the general population. 0 1995 Wiley-Liss, Inc.