title: Characterization of a recurrent novel large duplication in the cystic fibrosis transmembrane conductance regulator gene.
abstract: Recently, DNA rearrangements in the cystic fibrosis transmembrane conductance regulator (CFTR) gene have been described with increasing frequency. These large DNA rearrangements are not detected using conventional methods of DNA sequencing, single-strand conformational polymorphism, or denaturing high-performance liquid chromatography. We and others have described methods to detect such rearrangements in the CFTR gene. With one exception, all rearrangements reported thus far are single or multiple exon deletions, whereas only one report has described a large duplication. We describe here the detection and characterization of a novel large duplication in the CFTR gene. This duplication, referred to as gIVS6a + 415_IVS10 + 2987Dup26817bp, was detected in a classic CF female patient whose other mutation was DeltaF508. The duplication was inherited paternally. The duplication encompassed exons 6b to 10 and occurred on the IVS8-11TG/IVS8-7T/G1540 haplotype. This large duplication is predicted to result in the production of a truncated CFTR protein lacking the terminal part of NBD1 domain and beyond and thus can be considered a null allele. The combination of the DeltaF508 and gIVS6a + 415_IVS10 + 2987Dup26817bp mutation probably causes the severe CF phenotype in this patient. We designed a simple polymerase chain reaction test to detect the duplication, and we further detected the same duplication from another independent laboratory. The duplication breakpoint is identical in all three patients, suggesting a likely founder mutation.
authors: Quest Diagnostics Nichols Institute, Molecular Genetics, 33608 Ortega Hwy, San Juan Capistrano, CA 92690, USA. feras.x.hantash@questdiagnostics.com
authors: Feras M
authors: FM
authors: Hantash
authors: Joy B
authors: JB
authors: Redman
authors: Dana
authors: D
authors: Goos
authors: Anja
authors: A
authors: Kammesheidt
authors: Matthew J
authors: MJ
authors: McGinniss
authors: Weimin
authors: W
authors: Sun
authors: Charles M
authors: CM
authors: Strom
mesh_terms: D000328:Adult; D001483:Base Sequence; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D005453:Fluorescence; D020440:Gene Duplication; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator
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