The very low penetrance of cystic fibrosis for the R117H mutation: a reappraisal for genetic counselling and newborn screening.

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. The allelic prevalences of R117H (p(R117H)), on either intron 8 T5 or T7 background, and F508del (p(F508del)) were determined in the French population, to permit an evaluation of the penetrance of CF for the [R117H]+[F508del] genotype. RESULTS: Clinical details were documented for 184 [R117H]+[F508del] individuals, including 72 newborns. The disease phenotype was predominantly mild; one child had classical CF, and three adults' severe pulmonary symptoms. In 5245 healthy adults, p(F508del) was 1.06%, p(R117H;T7) 0.27% and p(R117H;T5)<0.01%. The theoretical number of [R117H;T7]+[F508del] individuals in the French population was estimated at 3650, whereas only 112 were known with CF related symptoms (3.1%). The penetrance of classical CF for [R117H;T7]+[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 CONCLUSIONS: These results suggest that R117H should be withdrawn from CF mutation panels used for screening programmes.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.

[Outcome evaluation of education in asthmatic children: the Robert-Debré hospital's experience]. / Impact de l'action éducative des enfants asthmatiques: l'expérience de l'hôpital Robert-Debré.

INTRODUCTION: Asthma, the most frequent chronic disease in childhood, is often treated by a continuous preventive treatment associated to the treatment of attacks. This therapeutic scheme fits well with educative skills. The Robert Debré's asthma school has been created in December 1999. Two nurses specialized in child asthma education are working in the school, helped by the pediatric pulmonologists. Children 6-year-old or more, that are treated in the hospital for asthma may be sent to the asthma school for education. They receive individual or collective education for cognitive, psycho-affective and sensory-motor targets related to asthma. AIM OF THE STUDY: To evaluate the outcome of educative action in childhood asthma and to study hospitalizations costs. SUBJECTS: children who received education for the first time in the year 2000 or 2001 and in whom exhaustive computerized data were available were eligible for the study. METHODS: retrospective and comparative study one-year-before/one-year-after the first educational intervention, assessed by comparison of the numbers of scheduled medical consultations and hospitalizations (and their cost). RESULTS: Sixty-six children were studied. We registered a significant increase of scheduled medical consultations (177 vs. 223; P < 0.03), and a very significant decrease of hospitalizations for asthma attacks (32 vs. 11; P < 0.001) without influence of the number of educational interventions and with a 52% decrease in costs (84,788 vs. 40,073 euros; P < 0.03). CONCLUSION: Asthmatic children education is a useful tool to improve medical follow-up and to decrease hospitalizations number. In a two-year survey, the decrease of cost in a group of 66 children is 44,715 euros.