title: Intragenic CFTR Duplication and 5T/12TG Variant in a Patient with Non-Classic Cystic Fibrosis.
abstract: Cystic fibrosis (CF) is an autosomal recessive disorder characterized by the accumulation of sticky and heavy mucus that can damage several organs. CF shows variable expressivity in affected individuals, but it typically causes respiratory and digestive complications as well as congenital bilateral absence of the vas deferens in males. Individuals with classic CF usually have variants that produce a defective protein from both alleles of the CFTR gene. Individuals with other variants may present with classic, non-classic, or milder forms of CF due to lower levels of functional CFTR protein. This article reports the genetic analysis of a female with features of asthma and mild or non-classic CF. CFTR sequencing demonstrated that she is a carrier for a maternally derived 5T/12TG variant. Deletion/duplication analysis by multiplex ligation-dependent probe amplification (MLPA) showed the presence of an intragenic paternally derived duplication involving exons 7-11 of the CFTR gene. This duplication is predicted to result in the production of a truncated CFTR protein lacking the terminal part of the nucleotide-binding domain 1 (NBD1) and thus is likely to be a non-functioning allele. The combination of this large intragenic duplication and 5T/12TG is the probable cause of the mild or non-classic CF features in this individual.
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: Patricia B S
authors.initials: PB
authors.lastname: Celestino-Soper
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Simpson
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: Danika
authors.initials: D
authors.lastname: Tumbleson Brink
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: Ty C
authors.initials: TC
authors.lastname: Lynnes
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Dlouhy
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.|Krannert Institute of Cardiology, Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: Matteo
authors.initials: M
authors.lastname: Vatta
authors.affiliation: Division of Pulmonary, Allergy, Critical Care, Occupational, and Sleep Medicine, Indiana University, Indianapolis, IN, 46202, USA.
authors.forename: Jana
authors.initials: J
authors.lastname: Yeley
authors.affiliation: Division of Pulmonary, Allergy, Critical Care, Occupational, and Sleep Medicine, Indiana University, Indianapolis, IN, 46202, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Brown
authors.affiliation: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
authors.forename: Shaochun
authors.initials: S
authors.lastname: Bai
mesh_terms: D000328:Adult; D003550:Cystic Fibrosis / Q000235:genetics* / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D016254:Mutagenesis, Insertional; D000072417:Protein Domains
chemical_list: C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator