Prevalence Of Cystic Fibrosis Research Articles

CFTR H609R mutation in Ecuadorian patients with cystic fibrosis

Mutation epidemiology in each ethnic group is important for cystic fibrosis diagnosis and genetic counselling. To date, little has been reported on the prevalence of cystic fibrosis in the Ecuadorian population where the mutation distribution appears to differ from that of Europe. We present a series of four Ecuadorian patients homozygous for the H609R mutation in the CFTR gene. This is the first report of detection of this mutation in the Ecuadorian population. Taking advantage of the homozygous status of the patients, an evaluation of the most important clinical parameters is presented. From the diagnostic point of view, the information provided by our study is of relevance in designing an appropriate strategy for genetic testing of patients in Ecuador and in European countries where immigration from Ecuador is common.

Combined Pancreatic Islet-Lung Transplantation With Islet Percutaneous Portal Embolization in Cystic Fibrosis

Combined Pancreatic Islet-Lung Transplantation With Islet Percutaneous Portal Embolization in Cystic Fibrosis

Cystic fibrosis carrier frequency and estimated prevalence of the disease in Morocco

Background The epidemiology of cystic fibrosis (CF) is poorly known in North African populations, in particular in Morocco and the CF carrier frequency in the general Moroccan population has never been evaluated. Methods To estimate the prevalence of CF mutations in Morocco, blood samples from 150 healthy Moroccans were tested for frequent CFTR mutations and the intron 8 polyT variant. Results Two subjects were heterozygous for F508del and eight others for the (T)5 variant. Conclusion These findings indicate that the Moroccan population is at risk for CF and CFTR-related disorders. CF prevalence could be in the range of that found in European populations. Wider studies are necessary to identify the clinical pattern and accurately determine the prevalence and molecular basis of CF in Morocco.

The epidemiology of cystic fibrosis in the Western Cape Province

Objectives . To determine the incidence and prevalence of cystic fibrosis (CF) among populations of the Western Cape province of South Africa. Design and subjects . Descriptive study using data from a database of CF cases and the 1996 Census. Measures . CF births from 1987 to 1996 and known CF patients in 1996 were compared with Census birth data and population data, respectively. Results . The very small numbers of black African CF patients precluded estimating the epidemiology in this group. The incidences of CF for coloured and white patients were 1 in 9 845 and 1 in 2 853 live births, respectively. There was underascertainment of cases in non-metropolitan areas. The prevalence of CF per 100 000 of the population was 2.6 and 11 for the coloured and white populations, respectively. The estimated number of persons with CF in these two groups in South Africa in 2001 was 571. Conclusions . CF was more common in the coloured population and less common in the white population than previously estimated. Under-diagnosis occurred in non-metropolitan areas in both groups.

A Frequent Large Rearrangement in theCFTRGene in Cystic Fibrosis Patients from Reunion Island

Reunion Island is a French province, 800 km east of Madagascar and 200 km west of Mauritius. On Reunion Island, the birth prevalence of cystic fibrosis (CF) is particularly high in the population of European origin, approximately 1:1000. In a previous study, we demonstrated that the screening of the 27 exons of the CF transmembrane conductance regulator (CFTR) gene by denaturing high-pressure liquid chromatography (DHPLC) in 114 CF families allowed the detection of about 93% of the molecular defects present on Reunion Island. Unidentified CF mutations may lie in introns or in regulatory regions that are not routinely investigated, or may correspond to gene rearrangements such as large, heterozygous deletions that escape detection using current PCR-based techniques. Using a combination of different methods (such as multiplex ligation-dependent probe amplification), 6 of the 13 unidentified CF alleles (46%) were found to harbor a deletion of 5288 bp, spanning from exon 17a to 18. Identification and examination of the breakpoint sequences showed that this deletion is different from the 3120+1kbdel8.6Kb previously found in the Palestinian Arabs. The chromosomes bearing IVS16+3316_IVS18+644del5288 did not have a common extragenic haplotype. Clinical evaluation of homozygotes (2 unrelated patients) and compound heterozygotes indicated that this deletion represents a severe mutation associated with positive sweat chloride test, pancreatic insufficiency, and early age at diagnosis.

Mutational spectrum of cystic fibrosis patients from Córdoba province and its zone of influence: Implications of molecular diagnosis in Argentina

Cystic Fibrosis (CF) is an autosomal recessive disorder affecting 1/2000–4000 newborns in Caucasian populations. This lethal disease mainly affects respiratory and digestive organs as well as fertility in man. So far, the CF prevalence and mutational spectrum have showed specificity among populations and regions, making it necessary to establish them in each one. In this study, we present the spectrum and frequency of CFTR gene mutations in CF patients from Córdoba (a province with 3.1 millions inhabitants in the middle of Argentina) and its zone of influence, to offer an accurate genetic testing. The study includes 78 families in which 98 patients fulfilled clinical criteria to CF diagnosis. The strategy for the molecular diagnosis comprised analysis of 21 common mutations, microsatellite haplotypes and the complete CFTR gene analysis using scanning techniques followed by sequencing of the abnormal migration patterns. Our first step led us to the identification of 10 mutations that represented 76% of alleles. Another four mutations (p.R1066C, c.1811 + 1.6kbA > G, c.711 + 1G > T, and p.G85E) were found based on the microsatellite haplotype–mutation association. Finally, 14 mutations were characterized after the CFTR gene scanning, three of them are not previously described (p.G27R, c.622-2A > G, and p.W277R). In summary, we have identified 27 mutations accounting for 94.23% of CF alleles. This characteristic mutational spectrum highlights the 14 most frequent mutations (>1%) in the Córdoba region.

Carrier frequency of F508del mutation of cystic fibrosis in Indian population

Background: Cystic fibrosis (CF) is considered to be very rare in Indian subcontinent. Based on reports of CF in migrants from Indian subcontinent to United Kingdom and United States of America, the prevalence of CF is estimated to be between 1 / 10,000 and 1 / 40,000 in this ethnic group. The present study was done to estimate the carrier frequency of F508del mutation among neonates using cord blood samples to reflect the prevalence of CF in the study population. Methods: 955 mothers delivering at our hospital between December 1999 and November 2000 were enrolled. Cord blood samples were analyzed for F508del mutation using polymerase chain reaction and gel electrophoresis. The frequency of patients homozygous for F508del mutation in the population was estimated using Hardy–Weinberg principle. The prevalence of CF was estimated by using the proportion of F508del homozygous cases out of all CF patients, as reported in various studies (19–44%) from Indian subcontinent. Results: Out of 955 cord blood samples, 4 were positive for F508del mutation. The carrier frequency and gene frequency of F508del mutation in the Indian population was calculated to be 1 / 238 (0.42%) and 1 / 477 (0.21%), respectively. Frequency of CF patients homozygous for F508del mutation is 1 / 228,006. The estimated prevalence of CF is 1 / 43,321 to 1 / 100,323 in Indian population. Conclusion: CF does occur in Indian subcontinent though the prevalence is lesser than the Caucasian population.

Birth Prevalence and Survival in Cystic Fibrosis: A National Cohort Study in the Netherlands

Birth prevalence and survival in patients with cystic fibrosis (CF) in the Netherlands were last investigated > 30 years ago. However, since then the birth prevalence may have decreased because of genetic counseling and an increased number of newborns of non-European descent. Although survival of CF patients has increased worldwide, a significantly lower median age at death was recently reported in the Netherlands compared with data from the United States. To analyze birth prevalence and survival in CF patients in the Netherlands, and to compare this survival data with US CF data. Survey of all CF patients living in the Netherlands, and analysis of Dutch CF mortality statistics using data from the Dutch central statistics office, Statistics Netherlands (Voorburg, the Netherlands), and a comparison with Cystic Fibrosis Foundation (Bethesda, MD) patient registry data. All CF centers in the Netherlands and the United States. All CF patients treated in the Netherlands on January 1, 2001, and all persons who died of CF between 1974 and 2000, and an equivalent US population. Birth prevalence and birth cohort-specific survival. The overall birth prevalence of CF for 1974 to 1994 was 1 in 4,750 live births, which is a considerable decrease compared with 1961 to 1965 (1 in 3,600 live births). Estimated survival to 30 years increased from 6% in the 1950-to-1954 cohort, to 36% in the 1970-to-1973 cohort. Exact survival could be calculated from 1974 onwards. Survival to 15 years increased from 72% from the 1974-to-1979 cohort, to 91% in the 1985-to-1989 cohort. Survival in the United States in the 1980-to-1984 cohort was better compared to the Netherlands, but this difference has disappeared over subsequent cohorts. The actual birth prevalence of CF in the Netherlands is clearly lower than it was 30 years ago. Survival in CF has dramatically improved. The difference in survival between the Netherlands and the United States, as observed in the cohorts born > 20 years ago, has disappeared.

Review of outcomes of neonatal screening for cystic fibrosis versus non-screening in Europe

We reviewed the published results of European prospective cohort and controlled studies and 1 randomized controlled study to assess whether newborn screening (NBS) for cystic fibrosis (CF) leads to an improved prognosis. We used long-term survival, early mortality, nutritional and pulmonary status, and the number of hospital admissions as outcome measures. Effects on reproductive behavior of the parents and relatives were also assessed. In 2 studies, a similar trend for improved long-term survival rate of the screened cohort was observed, whereas in 2 other studies CF NBS appeared to prevent CF-related deaths in infancy and early childhood. Screened patients born in the last 2 decades showed normal growth for height and weight from infancy until late childhood. In most studies, patients who were screened were found to have less lung damage than their non-screened peers. CF NBS significantly reduced the number of affected children who ever required hospitalization. In Brittany, France, a reduction of 15.7% in CF prevalence at birth was attributed to the introduction of a NBS program for CF. We conclude that there is accumulating evidence that CF NBS prevents early CF-related deaths and leads to a substantial and prolonged health gain for patients with CF.

The prevalence and clinical characteristics of cystic fibrosis in South Asian Canadian immigrants

Background: Cystic fibrosis (CF) is considered to be rare among individuals from the Indian subcontinent. Furthermore, affected individuals are reported to experience a more severe clinical course. Aims: It was...

Impact of public health strategies on the birth prevalence of cystic fibrosis in Brittany, France.

Taking into account the situation of Brittany, a region of western France where cystic fibrosis (CF) is common and where a neonatal screening program was set up 14 years ago, the aim of this study was to determine the way in which the birth prevalence of CF has been influenced by the various public health strategies implemented in the region (neonatal screening, prenatal diagnosis, ultrasound examination and family testing). This study used the results of the neonatal screening program, which enabled a precise measure of the prevalence of CF at birth to be obtained. Over the same period, we collected data from prenatal diagnoses carried out in the region, first in families related to a CF child and also those made following the detection of an echogenic bowel upon routine ultrasound examination performed during pregnancy. The prevalence of CF at birth was estimated to be 1/2838 in the region over a 10-year period (1992-2001). By including the 54 CF-affected pregnancies that were terminated during these 10 years, the corrected birth prevalence of CF was 1/1972. Prenatal diagnosis was therefore responsible for a global decrease in CF prevalence at birth of 30.5%. This work constitutes the first study able to provide a precise measure of CF birth prevalence and of its evolution through the combined effects of neonatal screening, prenatal diagnosis, ultrasound examination and family testing.

Diabetic retinopathy in adult patients with cystic fibrosis-related diabetes

Cystic fibrosis-related diabetes is a well-recognized compli- cation in patients with cystic fibrosis. As patients with cystic fibrosis survive longer, the prevalence of cystic fibrosis- related diabetes will rise (1,2). Cystic fibrosis-related dia- betes has distinctive clinical and pathological features compared with non-cystic fibrosis-related diabetes (3). Microvascular complications, including diabetic retinopa- thy, were regarded as very rare in the past in these patients (4,5) and regular screening for diabetic retinopathy is not a universal practice in cystic fibrosis clinics in the U.K. Recently, cases of diabetic retinopathy have begun to emerge, mainly in patients with cystic fibrosis-related diabetes for 10 years or more (6,7). The aim of this study was to determine cross-sectionally the prevalence of dia- betic retinopathy in adult patients with cystic fibrosis- related diabetes for 5 yr or more who were attending a national cystic fibrosis centre in the U.K.

Neonatal screening for the cystic fibrosis main mutation delta F508 in Estonia.

In this pilot study the frequency of delta F508 mutation carriers, their geographic distribution, and the prevalence of cystic fibrosis (CF) in Estonia were investigated. During the screening programme 7396 newborns were tested for delta F508 mutation and 88 were found to carry this deletion. The mean frequency of delta F508 mutation carriers in Estonia was thus estimated as 1 out of 84 live births. In eight separate districts of Estonia the heterozygote frequencies differed significantly (p = 0.0369), with the highest incidence (1:36) on the Baltic Sea islands and western coastal region and with the lowest in south eastern parts of Estonia.

Identification of cystic fibrosis mutations in the United Arab Emirates

We have designed a study aimed at identifying the genetic mutations responsible for cystic fibrosis (CF) in the population of the United Arab Emirates. The prevalence of CF in the UAE is at least 1/15,000 live births and the disease is associated with very severe clinical presentations. We have investigated 17 unrelated families. Ten UAE national families were of Bedouin descent: all 15 CF patients, who presented with very severe forms of the disease, were homozygous for a S549R mutation due to a T→G transversion at nucleotide position 1779. Amongst a distinct population of Baluch origin, CF patients from 6 out of 7 affected families were DF508 homozyotes. Hence, the unique distribution of CF mutations in the United Arab Emirates - two mutations, S549R and DF508, characterize so far 94% of CF families - should allow efficient organizing and delivering of CF carrier screening programmes on the country's relatively limited population size. Hum Mutat 11:412–413, 1998. © 1998 Wiley-Liss, Inc.

Cystic fibrosis in children from ethnic minorities in the West Midlands

We have observed that Doctors often perceive that cystic fibrosis (CF) is exceptionally rare in non-whites, and that this bias has repeatedly resulted in diagnostic delay. We therefore compared the age at diagnosis, genetic features and relative prevalence of CF in non-whites and white patients in the West Midlands. Analysis of data on all CF patients diagnosed in childhood and stored in the West Midlands CF register. Sixteen of the 514 children on the register were not of white European extraction, comprising 13 patients whose families originated from the Indian subcontinent, two of mixed AfroCaribbean/white European extraction and one of mixed Pakistani/white European extraction. The median age of diagnosis was similar in the white European and non-white patients (0.42 vs. 0.33 years, 95% CI for the difference of the medians -0.15, 0.37). However, in five cases with typical clinical features the diagnosis appears to have been delayed because of the child's racial origin (median age of diagnosis 3.87 years), and in five others the diagnosis was obvious (two siblings with CF, three had meconium ileus). There was a degree of consanguinity in nine cases. Five patients were homozygous or heterozygous for the delta F508 mutation, but no mutation could be identified in the remaining 11 patients. The possibility of CF needs to be considered in any patient with relevant clinical problems, regardless of racial origin. These findings need to be considered when planning any mass population screening programme for CF.

Estimated risk of cross-infection with Pseudomonas aeruginosa in Danish cystic fibrosis patients.

During the period 1970-1987 the number of cystic fibrosis (CF) patients treated at the Danish CF Center increased from 54 to 226. The prevalence of patients with chronic P. aeruginosa infection (CF + P) increased from 35% to 59%, whereafter it decreased to 54%. The yearly incidence of new CF + P patients averaged 8.4% in 1970-1975, 17% in 1976-80, 6.5% in 1981-85, and 3% in 1986-87. These changes correlated to the increased "contact density" between CF + P and non-infected CF patients (CF-P) due to intensified treatment starting in 1976, and the reduced "contact density" due to separation of the two groups starting in 1981. The same trends were observed during an epidemic spread of a multiply resistant P. aeruginosa in the CF + P group, which was also interrupted by separation of two groups of patients, with and without the multiply resistant strain. The observed prevalences of CF + P in different age groups of patients are in accordance with a 20% incidence/year in patients older than three years. The highest probability of acquiring chronic P. aeruginosa infection was calculated to be 2%/day and the lowest 0.09%/day spent in the Centre. By employing a simple mathematical model of the spread of infectious diseases it can be shown, that the highest incidence of CF + P is present when the prevalence of CF + P is 20-80%, and that an increase in the total number of patients also increases the incidence of CF + P unless the patients are divided into smaller groups. The observations in the Danish CF Centre are in accordance with this model.

Cystic fibrosis in Jordan: a pilot study.

Cystic fibrosis (CF) was diagnosed in 12 children from a total of 15,314 children admitted to the Paediatric Department at Jordan University Hospital (JUH) over the period 1976-1980. A diagnosis of meconium ileus was made in five children. The remaining seven affected children were diagnosed clinically on the basis of recurrent chest problems, failure to thrive, positive family history and a high level of sweat chloride, range 72-115 mEq/l (mean 97.6 mEq/l). Five children died (41.7%); three of the group with meconium ileus died during the post-operative period and two of the other group died soon after the diagnosis was made. The cause of such a high mortality rate is multifactorial. As CF was only recently recognized in Jordan, it is believed that the prevalence of CF among Jordanian children is underestimated. CF is still a very serious illness that demands early diagnosis and an intensive programme of continuing care. Therefore, further prospective study to evaluate its prevalence and impact on child health in Jordan is urgently needed.

Epidemiology of cystic fibrosis: A review

Three main reasons have been advanced for the degree of ignorance and confusion surrounding epidemiologic measures of the incidence and prevalence of Cystic Fibrosis, (CF) [83]. 1. 1.—Relatively recent recognition of CF as a specific disease entity. 2. 2.—Wide range of clinical manifestations, presentation as a multisystem disease, and great natural variation in the severity of involvement of various organs. 3. 3.—Past difficulty in establishing a diagnosis based on sound laboratory evidence, this being largely due to the lack of a screening test that had gained wide acceptance among diagnosticians [84], and inaccuracies in the performance and interpretation of the sweat test [85]. In addition to these factors, there are a number of methodological deficiencies and questionable assumptions in several of the papers that have here been reviewed. It may be noteworthy that the two sets of authors whose research design most closely matched [58, 74] being aimed at providing multiple ascertainment of cases and cross-checks of validity, have arrived at nearly the same estimated incidence of this particular disorder ( 1 3700 and 1 3800 respectively). The issue of selection and diagnostic criteria is one that has important implications for epidemiologic studies of cystic fibrosis. Particularly in a disease like CF, where the spectrum of clinical manifestations and severity of involvement is so broad, estimates of incidence will vary according to the criteria by which cases are ascertained and included. A greater degree of uniformity in standards than has been employed in previous studies is necessary before comparisons can meaningfully be made. There are good grounds for regarding most estimates of CF incidence to be minimum confirmed figures, and this is particularly so where the research design ensures that multiple ascertainments of the same case will be identifiable. Higher estimates are made where several sources of error (respondent bias, generalization of hospital data to the wider population, multiple ascertainments of the same patient) are not recognised.