title: A new insertion/deletion of the cystic fibrosis transmembrane conductance regulator gene accounts for 3.4% of cystic fibrosis mutations in Sardinia: implications for population screening.
abstract: Previous studies performed on Sardinian patients affected by cystic fibrosis (CF) have led to the identification of molecular defects in 87 of 88 patients. Two mutations, the F508del and T338I, were quite prevalent and accounted for 50% and 20% of the molecular defects, respectively. T338I has been detected rarely in other populations, most likely because of the genetic isolation of Sardinians. In the present study, we have performed a molecular analysis of the CF gene in eight Sardinian patients in whom only a single mutation has been defined. Using DNA analyses (Southern blot, single nucleotide polymorphisms, microsatellite analyses, and Extra-Long polymerase chain reaction) selected to detect gross gene rearrangement and by using mRNA studies, we detected a novel mutation c.54-5811_164 + 2186del8108ins182 in six of the eight patients investigated. This mutation consists of a gross deletion of 8108 bp spanning exon 2 with an insertion of 182 bp at the deletion junction, between nucleotide 54-5811 of intron 1 (IVS1 nt16864) and nucleotide 164 + 2186 of intron 2 (IVS2 nt 2186). By including the novel mutation in our mutation panel we are now able to reach a 95% detection rate, thereby improving the process of carrier detection and genetic counseling in Sardinia.
authors.affiliation: Istituto di Neurogenetica e Neurofarmacologia, Consiglio Nazionale delle Ricerche, Cagliari, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Faà
authors.forename: Pietro Pellegrini
authors.initials: PP
authors.lastname: Bettoli
authors.forename: Maria
authors.initials: M
authors.lastname: Demurtas
authors.forename: Maurizio
authors.initials: M
authors.lastname: Zanda
authors.forename: Vincenzina
authors.initials: V
authors.lastname: Ferri
authors.forename: Antonio
authors.initials: A
authors.lastname: Cao
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Rosatelli
mesh_terms: D000483:Alleles; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004247:DNA / Q000032:analysis*; D004252:DNA Mutational Analysis; D005820:Genetic Testing; D006801:Humans; D007558:Italy; D009154:Mutation; D044382:Population Groups; D012313:RNA / Q000032:analysis*
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012313:RNA; D004247:DNA