p.Ser1235Arg should no longer be considered as a cystic fibrosis mutation: results from a large collaborative study

• Published in: European journal of human genetics : EJHG Vol. 19; no. 1; pp. 36 - 42
• Main Authors: René, Céline, Paulet, Damien, Girodon, Emmanuelle, Costa, Catherine, Lalau, Guy, Leclerc, Julie, Cabet-Bey, Faïza, Bienvenu, Thierry, Blayau, Martine, Iron, Albert, Mittre, Hervé, Feldmann, Delphine, Guittard, Caroline, Claustres, Mireille, Georges, Marie des
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.01.2011; Nature Publishing Group
• Subjects: 631/208/2489/144; 631/208/737; 692/700/228/2050/1510; Amino Acid Sequence; Arginine - genetics; Benign; Bioinformatics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Collaboration; Conductance; Congenital diseases; Cystic fibrosis; Cystic Fibrosis - diagnosis; Cystic Fibrosis - epidemiology; Cystic Fibrosis - genetics; Cystic fibrosis transmembrane conductance regulator; Cystic Fibrosis Transmembrane Conductance Regulator - chemistry; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Cytogenetics; Errors of metabolism; Family medical history; Female; Fibrosis; Fundamental and applied biological sciences. Psychology; Gene Expression; General aspects. Genetic counseling; Genes; Genetic counseling; Genetic screening; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Heterozygote; Human Genetics; Humans; Laboratories; Lung diseases; Male; Male Urogenital Diseases; Medical genetics; Medical sciences; Metabolic diseases; Miscellaneous hereditary metabolic disorders; Missense mutation; Models, Molecular; Molecular and cellular biology; Molecular Epidemiology; Molecular Sequence Data; Mutation; Mutation, Missense; Pancreatitis; Phenotypes; Pregnancy; Prenatal Diagnosis; Serine - genetics; Ultrasonic imaging; Urogenital Abnormalities - diagnosis; Urogenital Abnormalities - epidemiology; Urogenital Abnormalities - genetics; Vas deferens; Vas Deferens - abnormalities; France; genetic counseling; mutation; diagnosis; cystic fibrosis; Genetic counseling; Respiratory disease; Nitric oxide; Metabolic diseases; Digestive diseases; Genetics; Cystic fibrosis; Diagnosis; Mutation; Genetic disease; Pancreatic disease
• ISSN: 1018-4813; 1476-5438; 1476-5438
• DOI: 10.1038/ejhg.2010.137

Among the 1700 mutations reported in the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene, a missense mutation, p.Ser1235Arg, 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, 26 patients (5 having CF, 10 CBAVD (congenital bilateral absence of the vas deferens) and 11 with CF-like symptoms) and 14 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 >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, give several lines of evidence against an association of p.Ser1235Arg with CF or CBAVD.