title: N1303K (c.3909C>G) mutation and splicing: implication of its c.[744-33GATT(6); 869+11C>T] complex allele in CFTR exon 7 aberrant splicing.
abstract: Cystic Fibrosis is the most common recessive autosomal rare disease found in Caucasians. It is caused by mutations on the Cystic Fibrosis Transmembrane Conductance Regulator gene (CFTR) that encodes a protein located on the apical membrane of epithelial cells. c.3909C>G (p.Asn1303Lys, old nomenclature: N1303K) is one of the most common worldwide mutations. This mutation has been found at high frequencies in the Mediterranean countries with the highest frequency in the Lebanese population. Therefore, on the genetic level, we conducted a complete CFTR gene screening on c.3909C>G Lebanese patients. The complex allele c.[744-33GATT(6); 869+11C>T] was always associated with the c.3909C>G mutation in cis in the Lebanese population. In cellulo splicing studies, realized by hybrid minigene constructs, revealed no impact of the c.3909C>G mutation on the splicing process, whereas the associated complex allele induces minor exon skipping.
authors.affiliation: University of Poitiers, "Génétique Moléculaire de Maladies Rares", 86073 Poitiers, France.
authors.forename: Raëd
authors.initials: R
authors.lastname: Farhat
authors.affiliation: University of Poitiers, "Génétique Moléculaire de Maladies Rares", 86073 Poitiers, France.
authors.forename: Géraldine
authors.initials: G
authors.lastname: Puissesseau
authors.affiliation: University of Poitiers, "Génétique Moléculaire de Maladies Rares", 86073 Poitiers, France ; University of Alexandria, Department of Genetics, Aflaton Street, El-Shatby, Alexandria 21545, Egypt.
authors.forename: Ayman
authors.initials: A
authors.lastname: El-Seedy
authors.affiliation: University of Poitiers, "Génétique Moléculaire de Maladies Rares", 86073 Poitiers, France ; "Centre Hospitalier Universitaire de Poitiers", 86021 Poitiers, France.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Pasquet
authors.affiliation: University of Poitiers, 86000 Poitiers, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Adolphe
authors.affiliation: Saint Joseph University, "Unité de Génétique Médicale", Faculty of Medicine, Beirut 1104 2020, Lebanon.
authors.forename: Sandra
authors.initials: S
authors.lastname: Corbani
authors.affiliation: Saint Joseph University, "Unité de Génétique Médicale", Faculty of Medicine, Beirut 1104 2020, Lebanon.
authors.forename: André
authors.initials: A
authors.lastname: Megarbané
authors.affiliation: University of Poitiers, "Génétique Moléculaire de Maladies Rares", 86073 Poitiers, France ; "Centre Hospitalier Universitaire de Poitiers", 86021 Poitiers, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Kitzis
authors.affiliation: University of Poitiers, "Génétique Moléculaire de Maladies Rares", 86073 Poitiers, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Ladeveze
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D001483:Base Sequence; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons; D057809:HEK293 Cells; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D007861:Lebanon; D008969:Molecular Sequence Data; D009154:Mutation; D017354:Point Mutation; D012326:RNA Splicing / Q000235:genetics; D014162:Transfection
chemical_list: C505032:CFTR protein, human; D018076:DNA, Complementary; D019005:Cystic Fibrosis Transmembrane Conductance Regulator