The very low penetrance of cystic fibrosis for the R117H mutation: a reappraisal for genetic counselling and newborn screening
Identifieur interne : 001786 ( Istex/Curation ); précédent : 001785; suivant : 001787The very low penetrance of cystic fibrosis for the R117H mutation: a reappraisal for genetic counselling and newborn screening
Auteurs : C. Thauvin-Robinet [France] ; A. Munck [France] ; F. Huet [France] ; E. Génin [France] ; G. Bellis [France] ; E. Gautier [France] ; M-P Audrézet [France] ; C. Férec [France] ; G. Lalau [France] ; M Des Georges [France] ; M. Claustres [France] ; T. Bienvenu [France] ; B. Gérard [France] ; P. Boisseau [France] ; F. Cabet-Bey [France] ; D. Feldmann [France] ; C. Clavel [France] ; E. Bieth [France] ; A. Iron [France] ; B. Simon-Bouy [France] ; C. Costa [France] ; R. Medina [France] ; J. Leclerc [France] ; D. Hubert [France] ; R. Nové-Josserand [France] ; I. Sermet-Gaudelus [France] ; G. Rault [France] ; J. Flori [France] ; S. Leroy [France] ; N. Wizla [France] ; G. Bellon [France] ; A. Haloun [France] ; S. Perez-Martin [France] ; G. D Cremont [France] ; H. Corvol [France] ; A. Clément [France] ; E. Houssin [France] ; C. Binquet [France] ; C. Bonithon-Kopp [France] ; C. Alberti-Boulmé [France] ; M A Morris [Suisse] ; L. Faivre [France] ; M. Goossens [France] ; M. Roussey [France]Source :
- Journal of Medical Genetics [ 0022-2593 ] ; 2009-11.
Abstract
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 (pR117H), on either intron 8 T5 or T7 background, and F508del (pF508del) 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, pF508del was 1.06%, pR117H;T7 0.27% and pR117H;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.
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DOI: 10.1136/jmg.2009.067215
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Boisseau</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Service de Génétique Médicale, Laboratoire de Génétique Moléculaire, CHU Hôtel Dieu, Nantes, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de Génétique Médicale, Laboratoire de Génétique Moléculaire, CHU Hôtel Dieu, Nantes</wicri:regionArea></affiliation></author><author><name sortKey="Cabet Bey, F" sort="Cabet Bey, F" uniqKey="Cabet Bey F" first="F" last="Cabet-Bey">F. Cabet-Bey</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Service d’Endocrinologie Moléculaire et Maladies rares, Centre de Biologie et Pathologie Est, CHU de Lyon, Bron, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service d’Endocrinologie Moléculaire et Maladies rares, Centre de Biologie et Pathologie Est, CHU de Lyon, Bron</wicri:regionArea></affiliation></author><author><name sortKey="Feldmann, D" sort="Feldmann, D" uniqKey="Feldmann D" first="D" last="Feldmann">D. Feldmann</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Laboratoire de Biochimie et Biologie Moléculaire, Hôpital d’Enfants Armand Trousseau, APHP, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Biochimie et Biologie Moléculaire, Hôpital d’Enfants Armand Trousseau, APHP, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Clavel, C" sort="Clavel, C" uniqKey="Clavel C" first="C" last="Clavel">C. Clavel</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Laboratoire Pol Bouin, UF Biologie Cellulaire, Hôpital de la Maison Blanche, CHU de Reims, Reims, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire Pol Bouin, UF Biologie Cellulaire, Hôpital de la Maison Blanche, CHU de Reims, Reims</wicri:regionArea></affiliation></author><author><name sortKey="Bieth, E" sort="Bieth, E" uniqKey="Bieth E" first="E" last="Bieth">E. Bieth</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Service de Génétique Médicale, Hôpital Purpan, CHU de Toulouse, Toulouse, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de Génétique Médicale, Hôpital Purpan, CHU de Toulouse, Toulouse</wicri:regionArea></affiliation></author><author><name sortKey="Iron, A" sort="Iron, A" uniqKey="Iron A" first="A" last="Iron">A. Iron</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Laboratoire de Génétique Moléculaire, Groupe Hospitalier Pellegrin, CHU de Bordeaux, Bordeaux, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Génétique Moléculaire, Groupe Hospitalier Pellegrin, CHU de Bordeaux, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Simon Bouy, B" sort="Simon Bouy, B" uniqKey="Simon Bouy B" first="B" last="Simon-Bouy">B. Simon-Bouy</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Laboratoire SESEP, Centre hospitalier de Versailles, Le Chesnay, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire SESEP, Centre hospitalier de Versailles, Le Chesnay</wicri:regionArea></affiliation></author><author><name sortKey="Costa, C" sort="Costa, C" uniqKey="Costa C" first="C" last="Costa">C. Costa</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Service de Biochimie-Génétique et Inserm U955 équipe 11, Groupe Henri Mondor-Albert Chenevier, APHP, Créteil, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de Biochimie-Génétique et Inserm U955 équipe 11, Groupe Henri Mondor-Albert Chenevier, APHP, Créteil</wicri:regionArea></affiliation></author><author><name sortKey="Medina, R" sort="Medina, R" uniqKey="Medina R" first="R" last="Medina">R. Medina</name><affiliation wicri:level="1"><mods:affiliation>Service de Biochimie-Génétique et Inserm U955 équipe 11, Groupe Henri Mondor-Albert Chenevier, APHP, Créteil, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de Biochimie-Génétique et Inserm U955 équipe 11, Groupe Henri Mondor-Albert Chenevier, APHP, Créteil</wicri:regionArea></affiliation></author><author><name sortKey="Leclerc, J" sort="Leclerc, J" uniqKey="Leclerc J" first="J" last="Leclerc">J. Leclerc</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Pôle de Biochimie et Biologie Moléculaire, Centre de Biologie Pathologie, CHU de Lille, Lille, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Pôle de Biochimie et Biologie Moléculaire, Centre de Biologie Pathologie, CHU de Lille, Lille</wicri:regionArea></affiliation></author><author><name sortKey="Hubert, D" sort="Hubert, D" uniqKey="Hubert D" first="D" last="Hubert">D. Hubert</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Service de Pneumologie, Hôpital Cochin, APHP, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Service de Pneumologie, Hôpital Cochin, APHP, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Nove Josserand, R" sort="Nove Josserand, R" uniqKey="Nove Josserand R" first="R" last="Nové-Josserand">R. Nové-Josserand</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Service de Médecine interne, Centre hospitalier Lyon sud, Pierre-Bénite, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Service de Médecine interne, Centre hospitalier Lyon sud, Pierre-Bénite</wicri:regionArea></affiliation></author><author><name sortKey="Sermet Gaudelus, I" sort="Sermet Gaudelus, I" uniqKey="Sermet Gaudelus I" first="I" last="Sermet-Gaudelus">I. Sermet-Gaudelus</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Service de Pédiatrie générale, Hôpital Necker-Enfants-Malades, APHP, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Service de Pédiatrie générale, Hôpital Necker-Enfants-Malades, APHP, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Rault, G" sort="Rault, G" uniqKey="Rault G" first="G" last="Rault">G. Rault</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Centre de Perharidy, Roscoff, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Centre de Perharidy, Roscoff</wicri:regionArea></affiliation></author><author><name sortKey="Flori, J" sort="Flori, J" uniqKey="Flori J" first="J" last="Flori">J. Flori</name><affiliation wicri:level="1"><mods:affiliation>Service de Néonatologie, SIHCUS – CMCO, Schiltigheim, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de Néonatologie, SIHCUS – CMCO, Schiltigheim</wicri:regionArea></affiliation></author><author><name sortKey="Leroy, S" sort="Leroy, S" uniqKey="Leroy S" first="S" last="Leroy">S. Leroy</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Service de pneumologie et immunoallergologie, CHRU de Lille, Lille, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Service de pneumologie et immunoallergologie, CHRU de Lille, Lille</wicri:regionArea></affiliation></author><author><name sortKey="Wizla, N" sort="Wizla, N" uniqKey="Wizla N" first="N" last="Wizla">N. Wizla</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Clinique de pédiatrie, CHRU de Lille, Lille, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Clinique de pédiatrie, CHRU de Lille, Lille</wicri:regionArea></affiliation></author><author><name sortKey="Bellon, G" sort="Bellon, G" uniqKey="Bellon G" first="G" last="Bellon">G. Bellon</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM Lyon Pédiatrie, Groupement Hospitalier Lyon Est, Bron, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM Lyon Pédiatrie, Groupement Hospitalier Lyon Est, Bron</wicri:regionArea></affiliation></author><author><name sortKey="Haloun, A" sort="Haloun, A" uniqKey="Haloun A" first="A" last="Haloun">A. Haloun</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Unité de transplantation thoracique, CHU Hôpital Guillaume et René Laënnec, Nantes, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Unité de transplantation thoracique, CHU Hôpital Guillaume et René Laënnec, Nantes</wicri:regionArea></affiliation></author><author><name sortKey="Perez Martin, S" sort="Perez Martin, S" uniqKey="Perez Martin S" first="S" last="Perez-Martin">S. Perez-Martin</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM – Service de Pédiatrie 1, Hôpital d’Enfants, CHU Dijon, Dijon, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM – Service de Pédiatrie 1, Hôpital d’Enfants, CHU Dijon, Dijon</wicri:regionArea></affiliation></author><author><name sortKey="D Cremont, G" sort="D Cremont, G" uniqKey="D Cremont G" first="G" last="D Cremont">G. D Cremont</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Service de Pédiatrie, CHI de Créteil, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Service de Pédiatrie, CHI de Créteil</wicri:regionArea></affiliation></author><author><name sortKey="Corvol, H" sort="Corvol, H" uniqKey="Corvol H" first="H" last="Corvol">H. Corvol</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Service de pneumologie pédiatrique, Hôpital d’Enfants Armand-Trousseau, APHP, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Service de pneumologie pédiatrique, Hôpital d’Enfants Armand-Trousseau, APHP, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Clement, A" sort="Clement, A" uniqKey="Clement A" first="A" last="Clément">A. Clément</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Service de pneumologie pédiatrique, Hôpital d’Enfants Armand-Trousseau, APHP, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Service de pneumologie pédiatrique, Hôpital d’Enfants Armand-Trousseau, APHP, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Houssin, E" sort="Houssin, E" uniqKey="Houssin E" first="E" last="Houssin">E. Houssin</name><affiliation wicri:level="1"><mods:affiliation>AFDPHE, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>AFDPHE, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Binquet, C" sort="Binquet, C" uniqKey="Binquet C" first="C" last="Binquet">C. Binquet</name><affiliation wicri:level="1"><mods:affiliation>Unité INSERM U866 CIE1, Faculté de médecine de Dijon, CHU Dijon, Dijon, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité INSERM U866 CIE1, Faculté de médecine de Dijon, CHU Dijon, Dijon</wicri:regionArea></affiliation></author><author><name sortKey="Bonithon Kopp, C" sort="Bonithon Kopp, C" uniqKey="Bonithon Kopp C" first="C" last="Bonithon-Kopp">C. Bonithon-Kopp</name><affiliation wicri:level="1"><mods:affiliation>Unité INSERM U866 CIE1, Faculté de médecine de Dijon, CHU Dijon, Dijon, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité INSERM U866 CIE1, Faculté de médecine de Dijon, CHU Dijon, Dijon</wicri:regionArea></affiliation></author><author><name sortKey="Alberti Boulme, C" sort="Alberti Boulme, C" uniqKey="Alberti Boulme C" first="C" last="Alberti-Boulmé">C. Alberti-Boulmé</name><affiliation wicri:level="1"><mods:affiliation>Centre d’Epidémiologie Clinique, Hôpital Robert Debré, APHP, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre d’Epidémiologie Clinique, Hôpital Robert Debré, APHP, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Morris, M A" sort="Morris, M A" uniqKey="Morris M" first="M A" last="Morris">M A Morris</name><affiliation wicri:level="1"><mods:affiliation>Laboratoire de Diagnostic moléculaire, Service de Médecine Génétique, Hôpitaux Universitaires, Geneva, Switzerland</mods:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Laboratoire de Diagnostic moléculaire, Service de Médecine Génétique, Hôpitaux Universitaires, Geneva</wicri:regionArea></affiliation></author><author><name sortKey="Faivre, L" sort="Faivre, L" uniqKey="Faivre L" first="L" last="Faivre">L. Faivre</name><affiliation wicri:level="1"><mods:affiliation>Centre de Génétique, Hôpital d’Enfants, CHU de Dijon, Dijon, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre de Génétique, Hôpital d’Enfants, CHU de Dijon, Dijon</wicri:regionArea></affiliation></author><author><name sortKey="Goossens, M" sort="Goossens, M" uniqKey="Goossens M" first="M" last="Goossens">M. Goossens</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Service de Biochimie-Génétique et Inserm U955 équipe 11, Groupe Henri Mondor-Albert Chenevier, APHP, Créteil, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de Biochimie-Génétique et Inserm U955 équipe 11, Groupe Henri Mondor-Albert Chenevier, APHP, Créteil</wicri:regionArea></affiliation></author><author><name sortKey="Roussey, M" sort="Roussey, M" uniqKey="Roussey M" first="M" last="Roussey">M. Roussey</name><affiliation wicri:level="1"><mods:affiliation>AFDPHE, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>AFDPHE, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Département de médecine de l’enfant et de l’adolescent, CHU de Rennes - Hôpital Sud, Rennes, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Département de médecine de l’enfant et de l’adolescent, CHU de Rennes - Hôpital Sud, Rennes</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:B853A40FF6E3B3C23256CA6EE8F47DE83882C23D</idno><date when="2009" year="2009">2009</date><idno type="doi">10.1136/jmg.2009.067215</idno><idno type="url">https://api.istex.fr/document/B853A40FF6E3B3C23256CA6EE8F47DE83882C23D/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">001786</idno><idno type="wicri:Area/Istex/Curation">001786</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">The very low penetrance of cystic fibrosis for the R117H mutation: a reappraisal for genetic counselling and newborn screening</title><author><name sortKey="Thauvin Robinet, C" sort="Thauvin Robinet, C" uniqKey="Thauvin Robinet C" first="C" last="Thauvin-Robinet">C. Thauvin-Robinet</name><affiliation wicri:level="1"><mods:affiliation>Centre de Génétique, Hôpital d’Enfants, CHU de Dijon, Dijon, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre de Génétique, Hôpital d’Enfants, CHU de Dijon, Dijon</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation></author><author><name sortKey="Munck, A" sort="Munck, A" uniqKey="Munck A" first="A" last="Munck">A. Munck</name><affiliation wicri:level="1"><mods:affiliation>AFDPHE, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>AFDPHE, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Service de gastro-entérologie-mucoviscidose et nutrition pédiatriques, Hôpital Robert Debré, APHP, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Service de gastro-entérologie-mucoviscidose et nutrition pédiatriques, Hôpital Robert Debré, APHP, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Huet, F" sort="Huet, F" uniqKey="Huet F" first="F" last="Huet">F. Huet</name><affiliation wicri:level="1"><mods:affiliation>AFDPHE, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>AFDPHE, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM – Service de Pédiatrie 1, Hôpital d’Enfants, CHU Dijon, Dijon, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM – Service de Pédiatrie 1, Hôpital d’Enfants, CHU Dijon, Dijon</wicri:regionArea></affiliation></author><author><name sortKey="Genin, E" sort="Genin, E" uniqKey="Genin E" first="E" last="Génin">E. Génin</name><affiliation wicri:level="1"><mods:affiliation>Inserm U794 et Fondation Jean Dausset/CEPH, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Inserm U794 et Fondation Jean Dausset/CEPH, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Bellis, G" sort="Bellis, G" uniqKey="Bellis G" first="G" last="Bellis">G. Bellis</name><affiliation wicri:level="1"><mods:affiliation>INED, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>INED, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Gautier, E" sort="Gautier, E" uniqKey="Gautier E" first="E" last="Gautier">E. Gautier</name><affiliation wicri:level="1"><mods:affiliation>Unité INSERM U866 CIE1, Faculté de médecine de Dijon, CHU Dijon, Dijon, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité INSERM U866 CIE1, Faculté de médecine de Dijon, CHU Dijon, Dijon</wicri:regionArea></affiliation></author><author><name sortKey="Audrezet, M P" sort="Audrezet, M P" uniqKey="Audrezet M" first="M-P" last="Audrézet">M-P Audrézet</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Laboratoire de Génétique Moléculaire et d’Histocompatibilité, CHU de Brest, Brest, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Génétique Moléculaire et d’Histocompatibilité, CHU de Brest, Brest</wicri:regionArea></affiliation></author><author><name sortKey="Ferec, C" sort="Ferec, C" uniqKey="Ferec C" first="C" last="Férec">C. Férec</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Laboratoire de Génétique Moléculaire et d’Histocompatibilité, CHU de Brest, Brest, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Génétique Moléculaire et d’Histocompatibilité, CHU de Brest, Brest</wicri:regionArea></affiliation></author><author><name sortKey="Lalau, G" sort="Lalau, G" uniqKey="Lalau G" first="G" last="Lalau">G. Lalau</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Pôle de Biochimie et Biologie Moléculaire, Centre de Biologie Pathologie, CHU de Lille, Lille, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Pôle de Biochimie et Biologie Moléculaire, Centre de Biologie Pathologie, CHU de Lille, Lille</wicri:regionArea></affiliation></author><author><name sortKey="Georges, M Des" sort="Georges, M Des" uniqKey="Georges M" first="M Des" last="Georges">M Des Georges</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Laboratoire de Génétique Moléculaire, IURC, CHU de Montpellier, Montpellier, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Génétique Moléculaire, IURC, CHU de Montpellier, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Claustres, M" sort="Claustres, M" uniqKey="Claustres M" first="M" last="Claustres">M. Claustres</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Laboratoire de Génétique Moléculaire, IURC, CHU de Montpellier, Montpellier, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Génétique Moléculaire, IURC, CHU de Montpellier, Montpellier</wicri:regionArea></affiliation></author><author><name sortKey="Bienvenu, T" sort="Bienvenu, T" uniqKey="Bienvenu T" first="T" last="Bienvenu">T. Bienvenu</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Laboratoire de Biochimie-Génétique, Hôpital Cochin, APHP, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Biochimie-Génétique, Hôpital Cochin, APHP, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Gerard, B" sort="Gerard, B" uniqKey="Gerard B" first="B" last="Gérard">B. Gérard</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Laboratoire de Biochimie Génétique, Hôpital Robert Debré, APHP, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Biochimie Génétique, Hôpital Robert Debré, APHP, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Boisseau, P" sort="Boisseau, P" uniqKey="Boisseau P" first="P" last="Boisseau">P. Boisseau</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Service de Génétique Médicale, Laboratoire de Génétique Moléculaire, CHU Hôtel Dieu, Nantes, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de Génétique Médicale, Laboratoire de Génétique Moléculaire, CHU Hôtel Dieu, Nantes</wicri:regionArea></affiliation></author><author><name sortKey="Cabet Bey, F" sort="Cabet Bey, F" uniqKey="Cabet Bey F" first="F" last="Cabet-Bey">F. Cabet-Bey</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Service d’Endocrinologie Moléculaire et Maladies rares, Centre de Biologie et Pathologie Est, CHU de Lyon, Bron, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service d’Endocrinologie Moléculaire et Maladies rares, Centre de Biologie et Pathologie Est, CHU de Lyon, Bron</wicri:regionArea></affiliation></author><author><name sortKey="Feldmann, D" sort="Feldmann, D" uniqKey="Feldmann D" first="D" last="Feldmann">D. Feldmann</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Laboratoire de Biochimie et Biologie Moléculaire, Hôpital d’Enfants Armand Trousseau, APHP, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Biochimie et Biologie Moléculaire, Hôpital d’Enfants Armand Trousseau, APHP, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Clavel, C" sort="Clavel, C" uniqKey="Clavel C" first="C" last="Clavel">C. Clavel</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Laboratoire Pol Bouin, UF Biologie Cellulaire, Hôpital de la Maison Blanche, CHU de Reims, Reims, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire Pol Bouin, UF Biologie Cellulaire, Hôpital de la Maison Blanche, CHU de Reims, Reims</wicri:regionArea></affiliation></author><author><name sortKey="Bieth, E" sort="Bieth, E" uniqKey="Bieth E" first="E" last="Bieth">E. Bieth</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Service de Génétique Médicale, Hôpital Purpan, CHU de Toulouse, Toulouse, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de Génétique Médicale, Hôpital Purpan, CHU de Toulouse, Toulouse</wicri:regionArea></affiliation></author><author><name sortKey="Iron, A" sort="Iron, A" uniqKey="Iron A" first="A" last="Iron">A. Iron</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Laboratoire de Génétique Moléculaire, Groupe Hospitalier Pellegrin, CHU de Bordeaux, Bordeaux, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire de Génétique Moléculaire, Groupe Hospitalier Pellegrin, CHU de Bordeaux, Bordeaux</wicri:regionArea></affiliation></author><author><name sortKey="Simon Bouy, B" sort="Simon Bouy, B" uniqKey="Simon Bouy B" first="B" last="Simon-Bouy">B. Simon-Bouy</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Laboratoire SESEP, Centre hospitalier de Versailles, Le Chesnay, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Laboratoire SESEP, Centre hospitalier de Versailles, Le Chesnay</wicri:regionArea></affiliation></author><author><name sortKey="Costa, C" sort="Costa, C" uniqKey="Costa C" first="C" last="Costa">C. Costa</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Service de Biochimie-Génétique et Inserm U955 équipe 11, Groupe Henri Mondor-Albert Chenevier, APHP, Créteil, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de Biochimie-Génétique et Inserm U955 équipe 11, Groupe Henri Mondor-Albert Chenevier, APHP, Créteil</wicri:regionArea></affiliation></author><author><name sortKey="Medina, R" sort="Medina, R" uniqKey="Medina R" first="R" last="Medina">R. Medina</name><affiliation wicri:level="1"><mods:affiliation>Service de Biochimie-Génétique et Inserm U955 équipe 11, Groupe Henri Mondor-Albert Chenevier, APHP, Créteil, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de Biochimie-Génétique et Inserm U955 équipe 11, Groupe Henri Mondor-Albert Chenevier, APHP, Créteil</wicri:regionArea></affiliation></author><author><name sortKey="Leclerc, J" sort="Leclerc, J" uniqKey="Leclerc J" first="J" last="Leclerc">J. Leclerc</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Pôle de Biochimie et Biologie Moléculaire, Centre de Biologie Pathologie, CHU de Lille, Lille, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Pôle de Biochimie et Biologie Moléculaire, Centre de Biologie Pathologie, CHU de Lille, Lille</wicri:regionArea></affiliation></author><author><name sortKey="Hubert, D" sort="Hubert, D" uniqKey="Hubert D" first="D" last="Hubert">D. Hubert</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Service de Pneumologie, Hôpital Cochin, APHP, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Service de Pneumologie, Hôpital Cochin, APHP, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Nove Josserand, R" sort="Nove Josserand, R" uniqKey="Nove Josserand R" first="R" last="Nové-Josserand">R. Nové-Josserand</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Service de Médecine interne, Centre hospitalier Lyon sud, Pierre-Bénite, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Service de Médecine interne, Centre hospitalier Lyon sud, Pierre-Bénite</wicri:regionArea></affiliation></author><author><name sortKey="Sermet Gaudelus, I" sort="Sermet Gaudelus, I" uniqKey="Sermet Gaudelus I" first="I" last="Sermet-Gaudelus">I. Sermet-Gaudelus</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Service de Pédiatrie générale, Hôpital Necker-Enfants-Malades, APHP, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Service de Pédiatrie générale, Hôpital Necker-Enfants-Malades, APHP, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Rault, G" sort="Rault, G" uniqKey="Rault G" first="G" last="Rault">G. Rault</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Centre de Perharidy, Roscoff, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Centre de Perharidy, Roscoff</wicri:regionArea></affiliation></author><author><name sortKey="Flori, J" sort="Flori, J" uniqKey="Flori J" first="J" last="Flori">J. Flori</name><affiliation wicri:level="1"><mods:affiliation>Service de Néonatologie, SIHCUS – CMCO, Schiltigheim, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de Néonatologie, SIHCUS – CMCO, Schiltigheim</wicri:regionArea></affiliation></author><author><name sortKey="Leroy, S" sort="Leroy, S" uniqKey="Leroy S" first="S" last="Leroy">S. Leroy</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Service de pneumologie et immunoallergologie, CHRU de Lille, Lille, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Service de pneumologie et immunoallergologie, CHRU de Lille, Lille</wicri:regionArea></affiliation></author><author><name sortKey="Wizla, N" sort="Wizla, N" uniqKey="Wizla N" first="N" last="Wizla">N. Wizla</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Clinique de pédiatrie, CHRU de Lille, Lille, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Clinique de pédiatrie, CHRU de Lille, Lille</wicri:regionArea></affiliation></author><author><name sortKey="Bellon, G" sort="Bellon, G" uniqKey="Bellon G" first="G" last="Bellon">G. Bellon</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM Lyon Pédiatrie, Groupement Hospitalier Lyon Est, Bron, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM Lyon Pédiatrie, Groupement Hospitalier Lyon Est, Bron</wicri:regionArea></affiliation></author><author><name sortKey="Haloun, A" sort="Haloun, A" uniqKey="Haloun A" first="A" last="Haloun">A. Haloun</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Unité de transplantation thoracique, CHU Hôpital Guillaume et René Laënnec, Nantes, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Unité de transplantation thoracique, CHU Hôpital Guillaume et René Laënnec, Nantes</wicri:regionArea></affiliation></author><author><name sortKey="Perez Martin, S" sort="Perez Martin, S" uniqKey="Perez Martin S" first="S" last="Perez-Martin">S. Perez-Martin</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM – Service de Pédiatrie 1, Hôpital d’Enfants, CHU Dijon, Dijon, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM – Service de Pédiatrie 1, Hôpital d’Enfants, CHU Dijon, Dijon</wicri:regionArea></affiliation></author><author><name sortKey="D Cremont, G" sort="D Cremont, G" uniqKey="D Cremont G" first="G" last="D Cremont">G. D Cremont</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Service de Pédiatrie, CHI de Créteil, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Service de Pédiatrie, CHI de Créteil</wicri:regionArea></affiliation></author><author><name sortKey="Corvol, H" sort="Corvol, H" uniqKey="Corvol H" first="H" last="Corvol">H. Corvol</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Service de pneumologie pédiatrique, Hôpital d’Enfants Armand-Trousseau, APHP, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Service de pneumologie pédiatrique, Hôpital d’Enfants Armand-Trousseau, APHP, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Clement, A" sort="Clement, A" uniqKey="Clement A" first="A" last="Clément">A. Clément</name><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Service de pneumologie pédiatrique, Hôpital d’Enfants Armand-Trousseau, APHP, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Service de pneumologie pédiatrique, Hôpital d’Enfants Armand-Trousseau, APHP, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Houssin, E" sort="Houssin, E" uniqKey="Houssin E" first="E" last="Houssin">E. Houssin</name><affiliation wicri:level="1"><mods:affiliation>AFDPHE, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>AFDPHE, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Binquet, C" sort="Binquet, C" uniqKey="Binquet C" first="C" last="Binquet">C. Binquet</name><affiliation wicri:level="1"><mods:affiliation>Unité INSERM U866 CIE1, Faculté de médecine de Dijon, CHU Dijon, Dijon, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité INSERM U866 CIE1, Faculté de médecine de Dijon, CHU Dijon, Dijon</wicri:regionArea></affiliation></author><author><name sortKey="Bonithon Kopp, C" sort="Bonithon Kopp, C" uniqKey="Bonithon Kopp C" first="C" last="Bonithon-Kopp">C. Bonithon-Kopp</name><affiliation wicri:level="1"><mods:affiliation>Unité INSERM U866 CIE1, Faculté de médecine de Dijon, CHU Dijon, Dijon, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Unité INSERM U866 CIE1, Faculté de médecine de Dijon, CHU Dijon, Dijon</wicri:regionArea></affiliation></author><author><name sortKey="Alberti Boulme, C" sort="Alberti Boulme, C" uniqKey="Alberti Boulme C" first="C" last="Alberti-Boulmé">C. Alberti-Boulmé</name><affiliation wicri:level="1"><mods:affiliation>Centre d’Epidémiologie Clinique, Hôpital Robert Debré, APHP, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre d’Epidémiologie Clinique, Hôpital Robert Debré, APHP, Paris</wicri:regionArea></affiliation></author><author><name sortKey="Morris, M A" sort="Morris, M A" uniqKey="Morris M" first="M A" last="Morris">M A Morris</name><affiliation wicri:level="1"><mods:affiliation>Laboratoire de Diagnostic moléculaire, Service de Médecine Génétique, Hôpitaux Universitaires, Geneva, Switzerland</mods:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Laboratoire de Diagnostic moléculaire, Service de Médecine Génétique, Hôpitaux Universitaires, Geneva</wicri:regionArea></affiliation></author><author><name sortKey="Faivre, L" sort="Faivre, L" uniqKey="Faivre L" first="L" last="Faivre">L. Faivre</name><affiliation wicri:level="1"><mods:affiliation>Centre de Génétique, Hôpital d’Enfants, CHU de Dijon, Dijon, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Centre de Génétique, Hôpital d’Enfants, CHU de Dijon, Dijon</wicri:regionArea></affiliation></author><author><name sortKey="Goossens, M" sort="Goossens, M" uniqKey="Goossens M" first="M" last="Goossens">M. Goossens</name><affiliation wicri:level="1"><mods:affiliation>French CF Laboratory Network, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Laboratory Network</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Service de Biochimie-Génétique et Inserm U955 équipe 11, Groupe Henri Mondor-Albert Chenevier, APHP, Créteil, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Service de Biochimie-Génétique et Inserm U955 équipe 11, Groupe Henri Mondor-Albert Chenevier, APHP, Créteil</wicri:regionArea></affiliation></author><author><name sortKey="Roussey, M" sort="Roussey, M" uniqKey="Roussey M" first="M" last="Roussey">M. Roussey</name><affiliation wicri:level="1"><mods:affiliation>AFDPHE, Paris, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>AFDPHE, Paris</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>French CF Care Centres, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>French CF Care Centres</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>CRCM - Département de médecine de l’enfant et de l’adolescent, CHU de Rennes - Hôpital Sud, Rennes, France</mods:affiliation><country xml:lang="fr">France</country><wicri:regionArea>CRCM - Département de médecine de l’enfant et de l’adolescent, CHU de Rennes - Hôpital Sud, Rennes</wicri:regionArea></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Medical Genetics</title><title level="j" type="abbrev">J Med Genet</title><idno type="ISSN">0022-2593</idno><idno type="eISSN">1468-6244</idno><imprint><publisher>BMJ Publishing Group Ltd</publisher><date type="published" when="2009-11">2009-11</date><biblScope unit="volume">46</biblScope><biblScope unit="issue">11</biblScope><biblScope unit="page" from="752">752</biblScope></imprint><idno type="ISSN">0022-2593</idno></series><idno type="istex">B853A40FF6E3B3C23256CA6EE8F47DE83882C23D</idno><idno type="DOI">10.1136/jmg.2009.067215</idno><idno type="href">jmedgenet-46-752.pdf</idno><idno type="ArticleID">mg67215</idno><idno type="PMID">19880712</idno><idno type="local">jmedgenet;46/11/752</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-2593</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">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 (pR117H), on either intron 8 T5 or T7 background, and F508del (pF508del) 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, pF508del was 1.06%, pR117H;T7 0.27% and pR117H;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.</div></front></TEI></record>Pour manipuler ce document sous Unix (Dilib)
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