RESUMO
Celocentesis is a new sampling tool for prenatal diagnosis available from 7 weeks in case of couples at risk for genetic diseases. In this study, we reported the feasibility of earlier prenatal diagnosis by celocentesis in four cases of cystic fibrosis and one case of cystic fibrosis and ß-thalassemia co-inherited in the same fetus. Celomic fluids were aspired from the celomic cavity between 8+2 and 9+3 weeks of gestation and fetal cells were picked up by micromanipulator. Maternal DNA contamination was tested and target regions of fetal DNA containing parental pathogenetic variants of CFTR and HBB genes were amplified and sequenced. Four of the five fetuses resulted as being affected by cystic fibrosis and, in all cases, the women decided to interrupt the pregnancy. In the other case, the fetus presented a healthy carrier of cystic fibrosis. The results were confirmed in three cases on placental tissue. In one case, no abortive tissue was obtained. In the last case, the woman refused the prenatal diagnosis to confirm the celocentesis data; the pregnancy is ongoing without complications. This procedure provides prenatal diagnosis of monogenic diseases at least four weeks earlier than traditional procedures, reducing the anxiety of patients and providing the option for medical termination of the affected fetus at 8-10 weeks of gestation, which is less traumatic and safer than surgical termination in the second trimester.
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística , Diagnóstico Pré-Natal , Humanos , Fibrose Cística/genética , Fibrose Cística/diagnóstico , Feminino , Gravidez , Diagnóstico Pré-Natal/métodos , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Adulto , Talassemia beta/genética , Talassemia beta/diagnóstico , FetoRESUMO
BACKGROUND: A clinical heterogeneity was reported in patients with Cystic Fibrosis (CF) with the same CFTR genotype and between siblings with CF. METHODS: We investigated all clinical aspects in a cohort of 101 pairs of siblings with CF (including 6 triplets) followed since diagnosis. RESULTS: Severe lung disease had a 22.2% concordance in sib-pairs, occurred early and the FEV1% at 12 years was predictive of the severity of lung disease in the adulthood. Similarly, CF liver disease occurred early (median: 15 years) and showed a concordance of 27.8% in sib-pairs suggesting a scarce contribution of genetic factors; in fact, only 2/15 patients with liver disease in discordant sib-pairs had a deficiency of alpha-1-antitrypsin (a known modifier gene of CF liver phenotype). CF related diabetes was found in 22 pairs (in 6 in both the siblings). It occurred later (median: 32.5 years) and is strongly associated with liver disease. Colonization by P. aeruginosa and nasal polyposis that required surgery had a concordance > 50% in sib-pairs and were poorly correlated to other clinical parameters. The pancreatic status was highly concordant in pairs of siblings (i.e., 95.1%) but a different pancreatic status was observed in patients with the same CFTR mutations. This suggests a close relationship of the pancreatic status with the "whole" CFTR genotype, including mutations in regulatory regions that may modulate the levels of CFTR expression. Finally, a severe course of CF was evident in a number of patients with pancreatic sufficiency. CONCLUSIONS: Physicians involved in care of patients with CF and in genetic counseling must be aware of the clinical heterogeneity of CF even in sib-pairs that, at the state of the art, is difficult to explain.
Assuntos
Portador Sadio/microbiologia , Fibrose Cística/fisiopatologia , Diabetes Mellitus/etiologia , Insuficiência Pancreática Exócrina/etiologia , Hepatopatias/etiologia , Íleo Meconial/etiologia , Irmãos , Adolescente , Adulto , Criança , Fibrose Cística/complicações , Fibrose Cística/genética , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Feminino , Volume Expiratório Forçado , Genótipo , Humanos , Lactente , Recém-Nascido , Itália , Masculino , Pessoa de Meia-Idade , Mutação , Pólipos Nasais/complicações , Pólipos Nasais/cirurgia , Orofaringe/microbiologia , Fenótipo , Pseudomonas aeruginosa , Índice de Gravidade de Doença , Escarro/microbiologia , Adulto Jovem , alfa 1-Antitripsina/genéticaRESUMO
BACKGROUND & AIMS: Some studies have shown a direct relationship between nutritional status and survival in Cystic Fibrosis (CF) patients. Body wasting, defined as a percentage of the ideal body weight for age, has been shown to be an independent predictor of mortality in CF. With respect to height only two studies were performed and these studies suggested that stunting is an important determinant of survival but both did not adjust statistical analysis for confounding variables. We aimed at determining the association between stunting and risk of mortality in CF patients. METHODS: 393 CF patients older than 6 years of age, 95 deceased, as cases, and 298 live, as controls, were enrolled in a nested case-control study. Stunting was defined by a height percentile < 5th. We performed a multivariate statistical analysis including height percentile and the following possible confounding variables: age, gender, Body Mass Index (BMI), Forced Expiratory Volume in 1 s (FEV1), genotype, pancreatic status, CF-related diabetes, colonization with Pseudomonas aeruginosa and/or Burkholderia cepacia. RESULTS: In the adjusted analyses stunting (OR 2.22 [IC 95%1.10-4.46]), wasting (OR 5.27 [IC 95% 2.66-10.41]), and FEV1 < 40% of predicted (OR 10.60 [IC 95% 5.43-20.67]) resulted the covariates that significantly predict the risk of mortality. CONCLUSIONS: Our study shows, for the first time, that stunting is a significant and independent risk factor for mortality in CF patients, and warrants an intervention of nutritional rehabilitation. Considering that nutritional interventions in stunted patients should be prolonged, are invasive and expensive, and might affect self-esteem and body image, their efficacy should be fully assessed by Randomised Controlled Trials.
Assuntos
Estatura , Fibrose Cística/mortalidade , Adolescente , Adulto , Área Sob a Curva , Índice de Massa Corporal , Burkholderia cepacia , Estudos de Casos e Controles , Criança , Pré-Escolar , Fibrose Cística/fisiopatologia , Feminino , Volume Expiratório Forçado , Humanos , Modelos Logísticos , Masculino , Análise Multivariada , Estado Nutricional , Pseudomonas aeruginosa , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
BACKGROUND: Hypertonic saline inhalation has been shown to be effective in patients with cystic fibrosis and lung disease. However, adverse events including marked airway narrowing are reported and a bronchodilator must be given before the administration of the product. METHODS: We carried out a prospective, randomized, double-blind, parallel-group, controlled study of a hypertonic saline solution containing hyaluronic acid (Hyaneb) versus standard hypertonic saline therapy to assess whether the presence of hyaluronic acid would improve the tolerability of hypertonic saline. RESULTS AND CONCLUSIONS: The results showed that nebulized Hyaneb was more effective in reducing the need for ß(2) bronchodilators and caused a significant reduction in the incidence of adverse effects compared with nebulized hypertonic saline solution alone. Its safety profile indicates that Hyaneb can be used for the treatment of lung disease in cystic fibrosis.
Assuntos
Fibrose Cística/tratamento farmacológico , Ácido Hialurônico/uso terapêutico , Pneumopatias/tratamento farmacológico , Solução Salina Hipertônica/uso terapêutico , Adolescente , Adulto , Criança , Fibrose Cística/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/efeitos adversos , Pneumopatias/etiologia , Masculino , Nebulizadores e Vaporizadores , Estudos Prospectivos , Solução Salina Hipertônica/administração & dosagem , Solução Salina Hipertônica/efeitos adversos , Adulto JovemRESUMO
BACKGROUND: The identification of cystic fibrosis (CF) patients who are at greater risk of lung damage could be clinically valuable. Thus, we attempted to replicate previous findings and verify the possible association between three single nucleotide polymorphisms (SNPs c.-52G>A, c.-44C>G and c.-20G>A) in the 5' untranslated region (5' UTR) of the ß defensin 1 (DEFB1) gene and the CF pulmonary phenotype. METHODS: Genomic DNA from 92 Italian CF patients enrolled in different regional CF centres was extracted from peripheral blood and genotyped for DEFB1 SNPs using TaqMan(®) allele specific probes. In order to avoid genetic confounding causes that can account for CF phenotype variability, all patients were homozygous for the F508del CFTR mutation, and were then classified on the basis of clinical and functional data as mild lung phenotype (Mp, n=50) or severe lung phenotype patients (Sp, n=42). RESULTS: For the c.-20G>A SNP, the frequency of the A allele, as well as the AA genotype, were significantly more frequent in Mp than in Sp patients, and thus this was associated with a protective effect against severe pulmonary disease (OR=0.48 and 0.28, respectively). The effect of the c.-20G>A A allele is consistent with a recessive model, and the protective effect against Sp is exerted only when it is present in homozygosis. For the other two SNPs, no differences were observed as allelic and genotypic frequency in the two subgroups of CF patients. CONCLUSIONS: Our results, although necessary to be confirmed in larger and multiethnic populations, reinforce DEFB1 as a candidate modifier gene of the CF pulmonary phenotype.