Background: Cystic fibrosis (CF) is caused by compound heterozygosity or homozygosity of CF transmembrane conductance regulator gene (CFTR) mutations. Phenotypic variability associated with certain mutations makes genetic counselling difficult, notably for R117H, whose disease phenotype varies from asymptomatic to classical CF. The high frequency of R117H observed in CF newborn screening has also introduced diagnostic dilemmas. The aim of this study was to evaluate the disease penetrance for R117H in order to improve clinical practice. Methods: The phenotypes in all individuals identified in France as compound heterozygous for R117H and F508del, the most frequent CF mutation, were described. F508del] was estimated at 0.03% and that of severe CF in adulthood at 0.06%. Conclusions: These results suggest that R117H should be withdrawn from CF mutation panels used for screening programmes. The real impact of so-called disease mutations should be assessed before including them in newborn or preconceptional carrier screening programmes.Cystic fibrosis (CF, MIM 219700) is one of the most frequent life shortening autosomal recessive diseases, characterised in its classical form by chronic pulmonary obstruction and infections, pancreatic insufficiency, male infertility and elevated sweat chloride concentrations.
Until the year 2000, systematic cystic fibrosis (CF) neonatal screening was only performed in a few regions of France. The Brittany region began in 1989, but not the neighboring region of Loire-Atlantique. The present study compares the clinical evolution of both affected populations 10 years after screening was started. Although the 77 screened and 36 nonscreened children were followed in different CF centers, they were included in similar care protocols. The clinical characteristics at diagnosis and their evolution over a 10-year period of all the children affected with CF and born between January 1, 1989 and December 31, 1998, excluding those with meconium ileus, were compared. There were no significant differences in sex ratio, gestational age, anthropometric data at birth, frequency of deltaF508 homozygotes, proportion of pancreatic-insufficient patients, and mean age between the two populations. Age at diagnosis was lower in the screened group (38 days vs. 472 days, P < 10(-7)), as was the delay in supplementation with pancreatic enzymes (1.7 months vs.15.9 months, P < 10(-7)). The proportion of children who were hospitalized at least once was higher among the nonscreened than the screened patients (86% vs. 49%, P < 10(-4)). Z-scores for weight and height were significantly better in the screened population, not only in the first years of life, but also at 5 years old for height and 8 years old for weight. The Shwachman and Brasfield scores were higher among the screened children during the whole period of follow-up. No significant differences in colonization by Pseudomonas aeruginosa nor in lung function were found. Given the homogeneity in the characteristics and the follow-up of both populations, the benefits in terms of nutrition and clinical well-being of neonatal screening appear to be clear, thus confirming the advantages of its general implementation.
These findings highlight the need for careful monitoring of neurosensory functioning, weight, and long-term treatment adequacy throughout childhood and adulthood.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.