p.Ser1235Arg should no longer be considered as a Cystic Fibrosis mutation: results from a large collaborative study: p.Ser1235Arg is not associated with CF disease
| Autor: | Emmanuelle Girodon, Julie Leclerc, Faïza Cabet-Bey, Thierry Bienvenu, Albert Iron, Marie des Georges, Martine Blayau, Guy Lalau, Hervé Mittre, Delphine Feldmann, Mireille Claustres, Catherine Costa, Céline René, Damien Paulet, C. Guittard |
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| Přispěvatelé: | Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), INSERM U955, équipe 11, Service de Biochimie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre de Biologie Pathologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d'Endocrinologie Moléculaire et Maladies rares, Hospices Civils de Lyon (HCL), Service de biochimie et de génétique moléculaire [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de génétique clinique [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de biochimie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-hôpital Sud, Service de Biochimie et de Biologie Moléculaire [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU) |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Male
Models Molecular medicine.medical_specialty Heterozygote diagnosis Genetic counseling Population Molecular Sequence Data Mutation Missense Cystic Fibrosis Transmembrane Conductance Regulator Prenatal diagnosis Biology Compound heterozygosity Arginine Cystic fibrosis Gastroenterology Article cystic fibrosis 03 medical and health sciences Vas Deferens Male Urogenital Diseases Pregnancy Internal medicine Prenatal Diagnosis Genetics medicine Serine Missense mutation Humans Amino Acid Sequence education Genetics (clinical) 030304 developmental biology 0303 health sciences education.field_of_study Molecular Epidemiology genetic counseling 030305 genetics & heredity medicine.disease Cystic fibrosis transmembrane conductance regulator 3. Good health Urogenital Abnormalities Mutation (genetic algorithm) biology.protein Female mutation |
| Zdroj: | European Journal of Human Genetics European Journal of Human Genetics, 2010, ⟨10.1038/ejhg.2010.137⟩ European Journal of Human Genetics, Nature Publishing Group, 2010, ⟨10.1038/ejhg.2010.137⟩ |
| ISSN: | 1018-4813 1476-5438 |
| DOI: | 10.1038/ejhg.2010.137⟩ |
| Popis: | International audience; Among the 1700 mutations reported in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, a missense mutation, p.Ser1235Arg, initially reported in a CF patient with a second mutation (p.Gly628Arg) on the same allele, is a relatively frequent finding. To clarify its clinical significance, we collected data from 104 subjects heterozygous for the mutation p.Ser1235Arg from the French CF network, addressed for various indications including classical CF, atypical phenotypes or carrier screening in subjects with or without a family history. Among them, twenty-six patients (five having CF, ten CBAVD -Congenital Absence of the Vas Deferens- and eleven with CF-like symptoms) and fourteen healthy subjects were compound heterozygous for a second CFTR mutation. An exhaustive CFTR gene analysis identified a second mutation in cis of p.Ser1235Arg in all CF patients and in 81.8% CBAVD patients. Moreover, epidemiological data from more than 2100 individuals found a higher frequency of p.Ser1235Arg in the general population than in CF or CBAVD patients. These data, added to the fact that in silico analysis and functional assays suggest a benign nature of this substitution gives several lines of evidence against an association of p.Ser1235Arg with CF or CBAVD. |
| Databáze: | OpenAIRE |
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