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Intragenic CFTR Duplication and 5T/12TG Variant in a Patient with Non-Classic Cystic Fibrosis

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...

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Autores principales: Celestino-Soper, Patricia B. S., Simpson, Edward, Tumbleson Brink, Danika, Lynnes, Ty C., Dlouhy, Stephen, Vatta, Matteo, Yeley, Jana, Brown, Cynthia, Bai, Shaochun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5172161/
https://www.ncbi.nlm.nih.gov/pubmed/27996019
http://dx.doi.org/10.1038/srep38776
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author Celestino-Soper, Patricia B. S.
Simpson, Edward
Tumbleson Brink, Danika
Lynnes, Ty C.
Dlouhy, Stephen
Vatta, Matteo
Yeley, Jana
Brown, Cynthia
Bai, Shaochun
author_facet Celestino-Soper, Patricia B. S.
Simpson, Edward
Tumbleson Brink, Danika
Lynnes, Ty C.
Dlouhy, Stephen
Vatta, Matteo
Yeley, Jana
Brown, Cynthia
Bai, Shaochun
author_sort Celestino-Soper, Patricia B. S.
collection PubMed
description 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.
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spelling pubmed-51721612016-12-28 Intragenic CFTR Duplication and 5T/12TG Variant in a Patient with Non-Classic Cystic Fibrosis Celestino-Soper, Patricia B. S. Simpson, Edward Tumbleson Brink, Danika Lynnes, Ty C. Dlouhy, Stephen Vatta, Matteo Yeley, Jana Brown, Cynthia Bai, Shaochun Sci Rep Article 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. Nature Publishing Group 2016-12-20 /pmc/articles/PMC5172161/ /pubmed/27996019 http://dx.doi.org/10.1038/srep38776 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Celestino-Soper, Patricia B. S.
Simpson, Edward
Tumbleson Brink, Danika
Lynnes, Ty C.
Dlouhy, Stephen
Vatta, Matteo
Yeley, Jana
Brown, Cynthia
Bai, Shaochun
Intragenic CFTR Duplication and 5T/12TG Variant in a Patient with Non-Classic Cystic Fibrosis
title Intragenic CFTR Duplication and 5T/12TG Variant in a Patient with Non-Classic Cystic Fibrosis
title_full Intragenic CFTR Duplication and 5T/12TG Variant in a Patient with Non-Classic Cystic Fibrosis
title_fullStr Intragenic CFTR Duplication and 5T/12TG Variant in a Patient with Non-Classic Cystic Fibrosis
title_full_unstemmed Intragenic CFTR Duplication and 5T/12TG Variant in a Patient with Non-Classic Cystic Fibrosis
title_short Intragenic CFTR Duplication and 5T/12TG Variant in a Patient with Non-Classic Cystic Fibrosis
title_sort intragenic cftr duplication and 5t/12tg variant in a patient with non-classic cystic fibrosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5172161/
https://www.ncbi.nlm.nih.gov/pubmed/27996019
http://dx.doi.org/10.1038/srep38776
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