WS11.6 Newborn screening for cystic fibrosis: Rationale for p.Arg117His (R117H) removal from the CFTR mutation panel in France
| Autor: | David Cheillan, M.-P. Audrézet, Christel Thauvin-Robinet, D. Delmas, E. Girodon, Michel Roussey, Anne Munck |
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| Rok vydání: | 2015 |
| Předmět: |
Pulmonary and Respiratory Medicine
Newborn screening medicine.medical_specialty Pediatrics Sweat testing business.industry medicine.disease Cystic fibrosis Gastroenterology Second line Cftr mutation Internal medicine Pediatrics Perinatology and Child Health Mutation (genetic algorithm) medicine business |
| Zdroj: | Journal of Cystic Fibrosis. 14:S23 |
| ISSN: | 1569-1993 |
| Popis: | NBS is aimed at early pre-symptomatic diagnosis of severe inherited diseases. CF NBS in France is based on IRT/DNA (CF 30 Elucigene)/IRT [1]. Detection of babies carrying one non-CF causing mutation (e.g. R117H) is one of the most negative impacts of DNA analysis [2]. Objective To assess the relevance and feasibility of R117H removal (r). Methods a.Describe the NBS carrying at least one R117H (T5, T7); b.Explain the decision making process of R117Hr (simulation; CF centres' opinion; feasibility; AFDPHE decision). Results In 2002–2012: a.Among 8,420,082 NBS (0.56% screened positive), 6309 were referred for sweat testing (ST). Of these, 1531 had CF and 245 an inconclusive diagnosis (58% R117H). Considering those with at least one R117H and the ST, were identified 365 carriers with only one R117H and a negative (–) ST; 142 carrying 2 CF 30 mutations with at least one R117H all on a T7 background with (–), 30–59 and (+) ST values respectively in 74, 59 and 9 cases; b.With respect to decision making, 1.Simulation of R117Hr would prevent identification of 365 carriers and 12 R117H HZ (377/507; 75%); only 130 infants, carrying a non-R117H mutation would be referred for ST (130/507; 25%). Among them, 62 with (–) ST would be classified as carriers but 68 with ST ≥30 mmol/L would be further investigated. 2.CF teams favoured R117Hr (61%). 3.Elucigene confirmed feasibility and AFDPHE validated R117Hr. Conclusion In France, R117H exclusively found on a T7 background allowed R117Hr to minimize the negative impact of DNA analysis. In those with one CFTR mutation and ST ≥30 mmol/L, the search for other mutations will be required, with R117H included in the second line panel. |
| Databáze: | OpenAIRE |
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