RESUMEN
Physicians and physiotherapists who care for CF patients have recommended the use of trampolines as a physiotherapeutic tool for enhancing cardiopulmonary performance, encouraging sputum production, and improving general well-being. Despite some therapeutic and recreational benefits associated with trampoline use, papers in the general pediatric population mostly document an increased incidence of injuries, ranging from minor trauma to spinal cord injuries and even death. The aim of this review is to examine the accumulated published data regarding the use of trampolines, to assess their potential contributions and disadvantages for CF patients, and to define whether trampoline use should be recommended. An extensive search in the published medical literature retrieved approximately 60 articles that primarily dealt with trampolines, out of which only two dealt with CF. The preponderance of these articles are reports pertaining to injuries related to the use of trampolines, with only a few describing the medical, physiologic, and/or psychological benefits of trampolines. Based on the accumulated data, the presumed benefits of trampoline use for CF patients are not proven. Furthermore, the suggested benefits could be acquired using other types of exercise. Weighing the known risks of trampolines against the potential benefits that are not unique to this modality suggests that the use of trampolines for CF should not be recommended.
Asunto(s)
Fibrosis Quística/rehabilitación , Terapia por Ejercicio , Modalidades de Fisioterapia , Heridas y Lesiones/epidemiología , Heridas y Lesiones/etiología , Adolescente , Adulto , Niño , Ensayos Clínicos como Asunto , Diseño de Equipo , Terapia por Ejercicio/efectos adversos , Terapia por Ejercicio/métodos , Estado de Salud , Humanos , Modalidades de Fisioterapia/efectos adversos , Factores de Riesgo , Seguridad , Deportes , Resultado del TratamientoRESUMEN
Patients with normal or borderline sweat tests present a diagnostic challenge. In spite of the availability of genetic analysis and measurement of nasal potential difference, there is still uncertainty in diagnosing cystic fibrosis in some patients. CA 19-9 is a tumor-associated antigen whose levels were previously found to be elevated in some cystic fibrosis patients. We investigated whether serum CA 19-9 levels can contribute to establishing the diagnosis of cystic fibrosis in patients with a borderline sweat test, and evaluated the influence of different clinical variables on CA 19-9 levels. Serum CA 19-9 levels were measured in 82 cystic fibrosis patients grouped according to their genotype and in 38 healthy individuals. Group A included 50 patients who carried two mutations previously found to be associated with a pathological sweat test and pancreatic insufficiency (DeltaF508, W1282X, G542X, N1303K, and S549R). Group B included 13 compound heterozygote cystic fibrosis patients who carried one mutation known to cause mild disease with a borderline or normal sweat test and pancreatic sufficiency (3849+10kb C-->T, 5T). Group C included 38 normal controls. Nineteen cystic fibrosis patients carried at least one unidentified mutation. An association between CA 19-9 levels and age, pulmonary function, pancreatic status, sweat chloride, previous pancreatitis, serum lipase, meconium ileus, distal intestinal obstruction, liver disease, and diabetes was investigated. The distribution of CA 19-9 levels was significantly different between the three groups ( p<0.01); high CA 19-9 levels were found in 60% (30/50) of group Apatients and in 46.6% (6/13) of group B patients, but in only 5.2% (2/38) of the controls. CA 19-9 levels were inversely related to forced expiratory volume in 1 s, while no association was found with the other clinical parameters examined. Our findings suggest that the serum CA 19-9 in cystic fibrosis patients originates in the respiratory system, and has a useful ancillary role, particularly when diagnostic uncertainty exists. Hence, the diagnosis of cystic fibrosis should be considered in patients with borderline sweat tests and high CA 19-9 levels, but normal levels do not exclude cystic fibrosis.
Asunto(s)
Antígeno CA-19-9/sangre , Fibrosis Quística/diagnóstico , Electrólitos/análisis , Sudor/química , Adolescente , Adulto , Niño , Fibrosis Quística/sangre , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/fisiología , Humanos , MutaciónRESUMEN
Lung transplantation (Tx) is an optional treatment for cystic fibrosis (CF) patients with end-stage lung disease. The decision to place a patient on the Tx waiting list is frequently complex, difficult, and controversial. This study evaluated the current criteria for lung Tx and assessed additional parameters that may identify CF patients at high risk of death. Data were extracted from the medical records of 392 CF patients. Forty of these patients had a forced expiratory volume in 1 s (FEV(1)) less than 30% predicted, and nine of these 40 patients were transplanted. A comparison was performed between the survival of those transplanted (n = 9) and those not transplanted (n = 31), by means of Kaplan-Meier survival curves. The influence on survival of age, gender, nutritional status, sputum aspergillus, diabetes mellitus, recurrent hemoptysis, oxygen use, and the decline rate of FEV(1), were investigated by means of univariate and multivariate analyses. The rate of decline of FEV(1) was evaluated employing the linear regression model. CF patients with a FEV(1)< 30% and who did not receive a lung transplant had survived longer than CF patients who did receive a lung transplant (median survival 7.33 vs. 3.49 yr, 5-yr survival 73% vs. 29%). Two factors--rate of decline in FEV(1) values and age < 15 yr--were found to influence the mortality rate, while the other parameters examined did not. Our results indicate that the current criterion of FEV(1)< 30% predicted, alone is not sufficiently sensitive to predict the mortality rate in CF patients and time of referral for Tx, as many of these patients survive for long periods of time. Additional criteria to FEV(1)< 30%, should include rapidly declining FEV(1) values and age < 15 yr.
Asunto(s)
Fibrosis Quística/mortalidad , Fibrosis Quística/cirugía , Trasplante de Pulmón , Selección de Paciente , Adolescente , Fibrosis Quística/fisiopatología , Femenino , Volumen Espiratorio Forzado , Humanos , Modelos Lineales , Masculino , Pronóstico , Modelos de Riesgos Proporcionales , Derivación y Consulta , Análisis de SupervivenciaRESUMEN
The diagnosis of cystic fibrosis (CF) is based on characteristic clinical and laboratory findings. However, a subgroup of patients present with an atypical phenotype that comprises partial CF phenotype, borderline sweat tests and one or even no common cystic fibrosis transmembrane conductance regulator (CFTR) mutations. The aim of this study was to evaluate the role of nasal potential difference (PD) measurements in the diagnosis of CF patients with an atypical presentation and in a population of patients suspected to have CF. Nasal PD was measured in 162 patients from four different groups: patients with classical CF (n = 31), atypical phenotype (n = 11), controls (n = 50), and patients with questionable CF (n = 70). The parameter, or combination of nasal PD parameters was calculated in order to best discriminate all CF patients (including atypical CF) from the non-CF group. The patients with atypical CF disease had intermediate values of PD measurements between the CF and non-CF groups. The best discriminate model that assigned all atypical CF patients as CF used: e(response to chloride-free and isoproterenol/response to amiloride) with a cut-off >0.70 to predict a CF diagnosis. When this model was applied to the group of 70 patients with questionable CF, 24 patients had abnormal PD similar to the atypical CF group. These patients had higher levels of sweat chloride concentration and increased rate of CFTR mutations. Nasal potential difference is useful in diagnosis of patients with atypical cystic fibrosis. Taking into account both the sodium and chloride transport elements of the potential difference allows for better differentiation between atypical cystic fibrosis and noncystic fibrosis patients. This calculation may assist in the diagnostic work-up of patients whose diagnosis is questionable.
Asunto(s)
Fibrosis Quística/diagnóstico , Potenciales de la Membrana/fisiología , Mucosa Nasal/fisiopatología , Adolescente , Adulto , Fibrosis Quística/genética , Fibrosis Quística/fisiopatología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Femenino , Genotipo , Humanos , Masculino , Fenotipo , Valor Predictivo de las Pruebas , Valores de ReferenciaRESUMEN
Patients with normal or borderline sweat test present a diagnostic challenge. In spite of the availability of different methods such as genetic analysis and measurements of nasal potential difference, uncertainty in diagnosing cystic fibrosis (CF) in some patients still exists. Neonates with CF have high serum lipase levels, which decline over time in pancreatic-insufficient patients, whereas pancreatic-sufficient patients demonstrate high serum lipase levels beyond infancy. Because patients with borderline or normal sweat test are almost always pancreatic sufficient, this study was aimed to assess whether serum lipase levels may be of help in establishing the diagnosis of CF in these patients. Serum lipase levels were measured in 100 CF patients and in 17 healthy individuals. Patients were grouped according to their genotype. Group A patients (n = 70) carried two mutations previously found to be associated with a pathologic sweat test and pancreatic insufficiency (delta F508, W1282X, G542X, N1303K, S549R). Group B (n = 30) were compound heterozygote patients who carried one mutation known to cause mild disease with borderline or normal sweat tests and pancreatic sufficiency (3849+10kb C-->T, 5T). Group C included 17 healthy controls. Serum lipase levels ranged between 2 and 104.4 U/L (mean +/- SD 16.9 +/- 14.7), 6.1-200 U/L (mean +/- SD 53.9 +/- 47.9), and 8.5-27.8 U/L (mean +/- SD 16.9 +/- 5.1) in Groups A, B, and C, respectively, with some overlapping between groups. The distribution of lipase levels was significantly different in Group B vs Groups A and C (P < 0.01). High lipase levels were found in 63.3% (19/30) of Group B patients, but in only 4.3% (3/70) and 0% (0/17) of Group A and C, respectively. Lipase levels were found to be inversely related to sweat chloride concentrations (r = -0.19, P < 0.05). Patients with borderline or normal sweat tests had high lipase levels, whereas low lipase levels were associated with pathologic sweat tests. Our findings indicate that the serum lipase level is genetically determined and that it has a useful role in the diagnosis of CF. Thus, in patients with borderline sweat tests and high lipase levels, the diagnosis of CF should be considered.
Asunto(s)
Fibrosis Quística/diagnóstico , Lipasa/sangre , Sudor/química , Adulto , Niño , Cloruros/análisis , Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/análisis , Insuficiencia Pancreática Exocrina/sangre , Humanos , Persona de Mediana EdadRESUMEN
The determination of endocrine and exocrine pancreatic function in cystic fibrosis patients is clinically important. Recently, a new non-invasive test, in which pancreatic stimulation by a Lundh meal is followed by sequential serum lipase measurements, was found to be a good indicator of exocrine pancreatic status. Since the Lundh meal also contains glucose, the present study assessed whether it also might be suitable for evaluation of the pancreatic endocrine axis. After an overnight fast, 10 healthy non-diabetic subjects and 14 cystic fibrosis patients ingested a Lundh meal. Glucose, insulin, and C peptide levels were measured at various time intervals following the meal. For purposes of comparison, the oral glucose tolerance test was also performed on the cystic fibrosis patients. All healthy subjects demonstrated an increase in glucose levels post Lundh meal, peaking at 45 min (mean 140+/-21 mg/dl) and then gradually declining and reaching the normal range at 120 min. Concordant peaks of insulin (46.3+/-20 IU/ml) and C peptide (5.8+/-1. 5 ng/ml) levels were noted at 60 min. All 14 cystic fibrosis patients had normal basal glucose levels: in 8, the pattern of glucose, insulin, and C peptide post Lundh meal was similar to that of the healthy controls. These 8 patients also had a normal oral glucose tolerance test, and their hemoglobin A(1C) levels were within the normal range. The other 6 cystic fibrosis patients demonstrated glucose levels above 200 mg/dl 30-60 min post Lundh meal, and all also had an impaired oral glucose tolerance test. Of these 6, 4 had high levels of hemoglobin A(1C). This study demonstrates that the Lundh meal challenges the endocrine pancreas as well as the oral glucose tolerance test. Thus, determination of both exocrine and endocrine pancreatic status can be achieved by a single non-invasive test.
Asunto(s)
Fibrosis Quística/diagnóstico , Fibrosis Quística/fisiopatología , Islotes Pancreáticos/fisiopatología , Páncreas/fisiopatología , Pruebas de Función Pancreática/métodos , Adolescente , Adulto , Glucemia/metabolismo , Péptido C/sangre , Estudios de Casos y Controles , Fibrosis Quística/sangre , Dieta , Estudios de Evaluación como Asunto , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/sangre , Masculino , Factores de TiempoRESUMEN
Determination of pancreatic function is essential in cystic fibrosis. The most-reliable method is by measuring pancreatic enzymes in the duodenum following intravenous or oral stimulation. However, this is invasive, time consuming, and expensive. Indirect tests are non-invasive but lack accuracy. This study examines a simple test which combines pancreatic stimulation by Lundh meal and sequential serum lipase measurements. The test was performed on three groups: group A, 36 cystic fibrosis patients carrying two mutations associated with severe disease and pancreatic insufficiency (delta F508, W1282X, G542X, N1303K, S549R); group B, 8 compound heterozygote cystic fibrosis patients carrying one mutation causing mild disease with pancreatic sufficiency (3849 + 10 kb C-->T); group C, 17 healthy individuals. Basal lipase levels were 2-16.5, 16.4-73, and 8.5-27.8 U/l in groups A, B, and C, respectively, with some overlapping between groups. There were three patterns of lipase activity (1) consistently low levels (group A) suggested a severely affected insufficient pancreas; (2) normal basal levels followed by a linear rise peaking 30 min after the meal (found in 16 of 17 healthy individuals and 3 patients of group B) reflecting an unaffected sufficient pancreas; (3) elevated lipase levels not influenced by the meal (5 patients of group B). This reflects an ongoing destructive process in the pancreas which will eventually result in conversion from pancreatic sufficiency to pancreatic insufficiency. Hence serum lipase activity prior to and 30 min after Lundh meal is a good indicator of pancreatic status allowing categorization of cystic fibrosis patients as pancreatic insufficient, pancreatic sufficient, or pancreatic sufficient with late conversion to insufficiency.
Asunto(s)
Fibrosis Quística/diagnóstico , Grasas de la Dieta/administración & dosificación , Lipasa/sangre , Páncreas/enzimología , Enfermedades Pancreáticas/diagnóstico , Adolescente , Adulto , Niño , Fibrosis Quística/metabolismo , Humanos , Enfermedades Pancreáticas/metabolismo , Pruebas de Función Pancreática , Periodo PosprandialRESUMEN
The syndrome of infantile bronchiolitis in cystic fibrosis (CF) carries a high mortality. Fifteen cases of CF encountered over the past 19 years with severe bronchiolitis with onset during the first 6 months of life are described. Treatment include steroids in high doses. All patients recovered. Further progress resembled the usual natural course of CF and showed no evidence of persisting lung damage. The mechanism of this syndrome is not clear and is probably dependent on many factors involved in early lung disease in CF. The frequency of severe bronchiolitis in cystic fibrosis may not be high, but it continues to be seen in clinical practice today.
Asunto(s)
Bronquiolitis/etiología , Fibrosis Quística/complicaciones , Fibrosis Quística/fisiopatología , Fibrosis Quística/terapia , Femenino , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
A 28-year-old female with cystic fibrosis presented with nephrotic syndrome and progressive renal failure. In addition, she complained of blurred vision and there was a purpuric skin eruption localized to her legs. A renal biopsy revealed fibrillary glomerulonephritis. Skin biopsy demonstrated swelling of capillary endothelium, thickening of arteriolar walls and deposition of IgA, C3 and fibrinogen by immunofluorescence. Opthalmoscopy and fluorescein angiography disclosed cotton wool spots with intraretinal haemorrhages and ischaemia of the macula. Albumin infusions resulted in worsening of eye symptoms and signs. The presence of these three clinicopathologic entities in a patient with CF may indicate the possibility of systemic involvement related to continued exposure to chronic bacterial lower lung infection.
Asunto(s)
Fibrosis Quística/complicaciones , Glomerulonefritis/complicaciones , Riñón/patología , Síndrome Nefrótico/complicaciones , Retina/patología , Piel/patología , Adulto , Biopsia , Fibrosis Quística/patología , Femenino , Técnica del Anticuerpo Fluorescente , Glomerulonefritis/patología , Humanos , Riñón/ultraestructura , Microscopía Electrónica , Síndrome Nefrótico/patología , Púrpura/etiología , Hemorragia Retiniana/etiologíaRESUMEN
Some patients express various features of cystic fibrosis (CF) even though essential characteristics of the disease might be absent. Such patients may suffer from respiratory disease without pancreatic insufficiency and normal sweat chloride levels. Others may present as male infertility because of congenital bilateral aplasia of the vas deferens (CBAVD) with no other signs of CF. The 5T allele, a DNA variant in a noncoding region of the cystic fibrosis transmembrane conductance regulator (CFTR) gene that reduces the level of the normal CFTR transcripts, was found in increased frequency among male patients with CBAVD. The purpose of this study was to investigate the possibility that the 5T allele is associated with dysfunction of organs other than the male reproductive system, leading to CF or atypical CF. Analysis of the 5T allele was performed on 148 subjects (29 with CF, 61 with atypical CF, and 58 with CBAVD) carrying 232 chromosomes with unidentified CFTR mutations, and on 142 non-CF chromosomes from healthy subjects of Ashkenazi origin. The frequency of the 5T allele among chromosomes from patients of Jewish Ashkenazi origin with CF and atypical CF (six of 33; 18%) was significantly higher than the frequency in the normal Ashkenazi population (eight of 142; 6%; p = 0.03). Analysis of the clinical presentation of the five patients with CF and the 12 patients with atypical CF carrying the 5T allele indicated that most patients suffered from respiratory disease presenting as asthma like symptoms, nasal polyposis, chronic sinusitis, chronic bronchitis, or bronchiectasis. Six patients had pancreatic insufficiency, two with meconium ileus. Sweat Cl- levels ranged from normal to elevated. Of the six male patients with respiratory disease who were old enough to be evaluated for fertility status, five were fertile and one had pancreatic insufficiency. Among male patients with CBAVD, 41% suffered from respiratory symptoms. Thus, the 5T allele is a variant with partial penetrance causing disease with an extreme variability of clinical presentation: from normal healthy fertile subjects or male patients with CBAVD to those with atypical or typical clinical phenotype of CF.
Asunto(s)
Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Fibrosis Quística/clasificación , Fibrosis Quística/genética , ADN Recombinante , Variación Genética , Adolescente , Adulto , Alelos , Niño , Preescolar , Femenino , Frecuencia de los Genes , Humanos , Judíos/genética , Masculino , MutaciónRESUMEN
The aim of this study was to evaluate the performance of anti-Helicobacter pylori (H. pylori) IgG antibodies in monitoring eradication of infection in children. Forty-seven H. pylori-infected children (aged 12.5 +/- 3.0 years, range 6.5-18 years) were followed for a mean of 30.3 months (range 6.66 months). Patients were divided into those with eradicated infection and those with ongoing infection, as determined by antral biopsy-related tests (histology, urease and culture). Anti-H. pylori antibodies (EIA) were tested at diagnosis and follow-up and changes of antibody titers were compared between the two groups. Twenty-five of 26 non-eradicated patients showed persistently high levels of antibodies throughout the study. One patient had non-detectable antibodies despite an ongoing infection for 12 months. Patients with eradicated infection showed a progressive fall of antibody levels from 52.9 +/- 32.4 U/ml at diagnosis to 17.5 +/- 4.1 U/ml at 6 months (p < 0.007) and 4.4 +/- 0.7 U/ml at > or = 12 months (p < 0.002). In 17 of 21 eradicated patients, serum antibodies normalized during the follow-up period; in 4 of the 21 patients, a decrease of > or = 40% of the initial value was observed during the 8-month follow-up. The validity of serology in the evaluation of H. pylori infection had a sensitivity of 100%, specificity of 96% and positive predictive and negative predictive values of 95% and 100% respectively. Our conclusion is that serial determination of anti-H. pylori antibodies is a reliable method for the follow-up and monitoring of H. pylori eradication in children and adolescents.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Monitoreo de Drogas/métodos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/inmunología , Helicobacter pylori/inmunología , Inmunoglobulina G/sangre , Adolescente , Factores de Edad , Niño , Monitoreo de Drogas/normas , Estudios de Seguimiento , Infecciones por Helicobacter/sangre , Humanos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Resultado del TratamientoRESUMEN
OBJECTIVE: Cystic fibrosis (CF) has variable clinical presentation. Disease severity is partially associated with the type of mutation. The aim of this study was to report genotype-phenotype analysis of the G85E mutation. PATIENTS: The phenotype of 12 patients (8 were from the same extended family, and 5 of them were siblings from 2 families) carrying at least one copy of the G85E mutation was evaluated and compared with the phenotype of 40 patients carrying the two severe mutations, W1282X and/or DeltaF508 (group 1), and with 20 patients carrying the splicing mutation, 3849+10kb C->T, which was found to be associated with milder disease (group 2). RESULTS: A high phenotypic variability was found among the patients carrying the G85E mutation. This high variability was found among patients carrying the same genotype and among siblings. All the studied chromosomes carrying the G85E mutation had the 7T variant in the polythymidine tract at the branch/acceptor site in intron 8. Of the G85E patients, 25% had pancreatic sufficiency and none had meconium ileus, compared with 0% and 32%, respectively, of patients from group 1, and 80% and 0%, respectively, from group 2. Two patients carrying the G85E mutation had sweat chloride levels <60 mmol/L whereas all the others had typically elevated levels >80 mmol/L. Compared with group 2, patients carrying the G85E mutation were diagnosed at an earlier age and had higher sweat chloride levels, with mean values similar to group 1 but significantly more variable. Forced expiratory volume in 1 second (FEV1) was similar in the three groups, with no differences in the slope or in age-adjusted mean values of FEV1. The levels of transcripts lacking exon 9 transcribed from the G85E allele measured in 3 patients were 55%, 49%, and 35% and their FEV1 values were 82%, 83%, and 50% predicated, respectively. CONCLUSIONS: The G85E mutation shows variable clinical presentation in all clinical parameters. This variability could be seen among patients carrying on the other chromosome the same CFTR mutation, and also among siblings. This variability is not associated with the level of exon 9 skipping. Thus, the G85E mutation cannot be classified either as a severe or as a mild mutation.
Asunto(s)
Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Fibrosis Quística/genética , Mutación , Edad de Inicio , Niño , Cloruros/análisis , Fibrosis Quística/clasificación , Fibrosis Quística/fisiopatología , Análisis Mutacional de ADN , Femenino , Volumen Espiratorio Forzado , Variación Genética , Genotipo , Humanos , Lactante , Masculino , Núcleo Familiar , Páncreas/fisiopatología , Fenotipo , Índice de Severidad de la Enfermedad , Sudor/química , Transcripción GenéticaRESUMEN
Children deficient in vitamin E have various neurologic symptoms. 2 cases representing different mechanisms of this vitamin deficiency are reported. A 15-year-old boy with fat malabsorption due to cystic fibrosis who was diagnosed as being vitamin E deficient (< 0.5 mg/l), had typical neuropathies. On the other hand, a 12-year-old Beduin girl had isolated vitamin E deficiency, as well as neurological symptoms suggestive of Friedrich's ataxia. Vitamin E supplementation by intramuscular injection in the first case and per os in the second led to significant improvement in neurological symptoms.
Asunto(s)
Enfermedades del Sistema Nervioso/etiología , Deficiencia de Vitamina E/complicaciones , Adolescente , Niño , Femenino , Ataxia de Friedreich/etiología , Humanos , Masculino , Vitamina E/uso terapéutico , Deficiencia de Vitamina E/terapiaAsunto(s)
Fibrosis Quística/terapia , Amilorida/uso terapéutico , Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/uso terapéutico , Desoxirribonucleasas/uso terapéutico , Humanos , Inhibidores de Proteasas/uso terapéutico , Uridina Trifosfato/uso terapéuticoRESUMEN
The incidence of cystic fibrosis (CF) and the frequency of disease-causing mutations varies among different ethnic and geographic populations. The Jewish population around the world is comprised of two major ethnic groups; Ashkenazi and non-Ashkenazi. The latter is further classified according to country of origin. In this study, we analyzed the incidence of CF and the distribution of CF mutations in the general Jewish population in Israel and in most of the Jewish ethnic subgroups. The disease frequency varies considerably among the latter. Among Ashkenazi Jews, the frequency of CF is 1:3300, which is similar to the frequency in most Caucasian populations. Among non-Ashkenazi Jews, the disease occurs at a similar frequency among Jews from Libya (1:2700), Georgia (1:2700), Greece and Bulgaria (1:2400), but is rare in Jews from Yemen (1:8800), Morocco (1:15000), Iraq (1:32000), and Iran (1:39000). So far, only 12 mutations have been identified in Israeli Jews, and this enables the identification of 91% of the CF chromosomes in the entire Jewish CF population. However, in each Jewish ethnic group, the disease is caused by a different repertoire of mutations. The frequency of identified mutations is high in Ashkenazi Jews (95%), and in Jews originating from Tunisia (100%), Libya (91%), Turkey (90%), and Georgia (88%). However, a lower frequency of mutations can be identified in Moroccan (85%), Egyptian (50%), and Yemenite (0%) Jews. For genetic counseling of a Jewish individual, it is necessary to calculate the residual risk according to ethnic origin. Carrier screening of healthy Jewish individuals is currently feasible for Ashkenazi Tunisian, Libyan, Turkish, and Georgian Jews. These results provide the required information for genetic counseling of Jewish CF families and screening programs of Jewish populations worldwide.
Asunto(s)
Fibrosis Quística/etnología , Fibrosis Quística/genética , Judíos/genética , Mutación , África del Norte/etnología , Asia/etnología , Europa (Continente)/etnología , Humanos , Incidencia , Israel/epidemiologíaRESUMEN
Behçet's disease, a multisystem disease is, by its nature, difficult to diagnose. The first manifestation of the disease may precede the appearance of other symptoms and signs essential for diagnosis by many years. In patients of Mediterranean origin, the early manifestations of the disease, may be confused with those of familial Mediterranean fever (FMF). Determination of HLA-B5 may, however, contribute to the diagnosis in children with partial manifestations of Beh,cet syndrome.
Asunto(s)
Síndrome de Behçet/diagnóstico , Antígenos HLA-B/análisis , Adolescente , Síndrome de Behçet/etnología , Síndrome de Behçet/inmunología , Niño , Diagnóstico Diferencial , Fiebre Mediterránea Familiar/diagnóstico , Femenino , Humanos , Lactante , Judíos , Masculino , Región Mediterránea , Medio Oriente , LinajeRESUMEN
The high frequency of mutations in the cystic fibrosis gene in patients with congenital bilateral absence of vas deferens (CBAVD) has raised the question whether all of them have a genital form of cystic fibrosis. We investigated 47 CBAVD patients by ultrasonography, 10 (21%) had renal malformations and 37 (79%) did not. In the former group, no cystic fibrosis mutations were found and sweat chloride concentrations were normal. In the latter group, 18 patients (49%) carried at least one cystic fibrosis mutation and sweat chloride was high in 17 of 26 tested (65%). Our findings suggest that CBAVD patients with renal malformations do not necessarily have cystic fibrosis.
Asunto(s)
Fibrosis Quística/genética , Riñón/anomalías , Conducto Deferente/anomalías , Humanos , Infertilidad Masculina/etiología , Riñón/diagnóstico por imagen , Masculino , Mutación , Ultrasonografía , Conducto Deferente/diagnóstico por imagenRESUMEN
The effect of nonsense mutations on mRNA levels is variable. The levels of some mRNAs are not affected and truncated proteins are produced, while the levels of others are severely decreased and null phenotypes are observed. The effect on mRNA levels is important for the understanding of phenotype-genotype association. Cystic fibrosis (CF) is a lethal autosomal recessive disease with variable clinical presentation. Recently, two CF patients with mild pulmonary disease carrying nonsense mutations (R553X, W1316X) were found to have severe deficiency of mRNA. In the Jewish Ashkenazi CF patient population, 60% of the chromosomes carry a nonsense mutation, W1282X. Patients homozygous for this mutation have severe disease presentation with variable pulmonary disease. The presence of CF transcripts in a group of patients homozygous and heterozygous for this mutation was studied by reverse transcriptase PCR of various regions of the gene. Subsequent hybridization to specific CF PCR probes and densitometry analysis indicated that the CF mRNA levels in patients homozygous for the W1282X mutation are not significantly decreased by the mutation. mRNA levels were compared for patients heterozygous for the W1282X mutation. The relative levels of mRNA with the W1282X, and the delta F508 or the normal alleles, were similar in each patient. These results indicate that the severe clinical phenotype of patients carrying the W1282X mutation is not due to a severe deficiency of mRNA. In addition, the severity, progression, and variability of the pulmonary disease are affected by other, as yet unknown factors.
Asunto(s)
Alelos , Fibrosis Quística/genética , Mutación , Mucosa Nasal/metabolismo , ARN Mensajero/análisis , Secuencia de Bases , Regulador de Conductancia de Transmembrana de Fibrosis Quística , Humanos , Proteínas de la Membrana/genética , Datos de Secuencia Molecular , Reacción en Cadena de la PolimerasaAsunto(s)
Fibrosis Quística/genética , Fibrosis Quística/etnología , Femenino , Genotipo , Humanos , Mutación , FenotipoRESUMEN
Different mutations in the cystic fibrosis (CF) gene appear to contribute to heterogeneity of the CF phenotype. We investigated 15 patients with CF who have the 3849 + 10 kb C-->T mutation. All were Ashkenazi Jews. Their clinical features were compared with those of CF patients with the delta F508/delta F508, W1282X/W1282X, W1282X/delta F508 mutations, which are known to be associated with a severe disease. Patients with the 3849 + 10 kb mutation were older, had been diagnosed as having CF at a more advanced age, and were in a better nutritional state. Sweat chloride values were normal (below 60 mmol/L) in 5 3849 + 10 kb patients (33%). 4 of these patients and 6 others (total 66%) had normal pancreatic function. However, age-adjusted pulmonary function did not differ between the two groups. None of the patients with 3849 + 10 kb C-->T had had meconium ileus or had liver disease or diabetes mellitus. We conclude that this mutation is associated with a mild type of CF.