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Things come in threes: A new complex allele and a novel deletion within the CFTR gene complicate an accurate diagnosis of cystic fibrosis
BACKGROUND: Despite consolidated guidelines, the clinical diagnosis and prognosis of cystic fibrosis (CF) is still challenging mainly because of the extensive phenotypic heterogeneity and the high number of CFTR variants, including their combinations as complex alleles. RESULTS: We report a family w...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9184661/ https://www.ncbi.nlm.nih.gov/pubmed/35348309 http://dx.doi.org/10.1002/mgg3.1926 |
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author | Persico, Ilaria Feresin, Agnese Faleschini, Michela Fontana, Giorgia Sirchia, Fabio Faletra, Flavio La Bianca, Martina Suergiu, Sarah Morgutti, Marcello Maschio, Massimo D'Adamo, Adamo Pio Raraigh, Karen S. Savoia, Anna Bottega, Roberta |
author_facet | Persico, Ilaria Feresin, Agnese Faleschini, Michela Fontana, Giorgia Sirchia, Fabio Faletra, Flavio La Bianca, Martina Suergiu, Sarah Morgutti, Marcello Maschio, Massimo D'Adamo, Adamo Pio Raraigh, Karen S. Savoia, Anna Bottega, Roberta |
author_sort | Persico, Ilaria |
collection | PubMed |
description | BACKGROUND: Despite consolidated guidelines, the clinical diagnosis and prognosis of cystic fibrosis (CF) is still challenging mainly because of the extensive phenotypic heterogeneity and the high number of CFTR variants, including their combinations as complex alleles. RESULTS: We report a family with a complicated syndromic phenotype, which led to the suspicion not only of CF, but of a dominantly inherited skeletal dysplasia (SD). Whereas the molecular basis of the SD was not clarified, segregation analysis was central to make a correct molecular diagnosis of CF, as it allowed to identify three CFTR variants encompassing two known maternal mutations and a novel paternal microdeletion. CONCLUSION: This case well illustrates possible pitfalls in the clinical and molecular diagnosis of CF; presence of complex phenotypes deflecting clinicians from appropriate CF recognition, and/or identification of two mutations assumed to be in trans but with an unconfirmed status, which underline the importance of an in‐depth molecular CFTR analysis. |
format | Online Article Text |
id | pubmed-9184661 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91846612022-06-14 Things come in threes: A new complex allele and a novel deletion within the CFTR gene complicate an accurate diagnosis of cystic fibrosis Persico, Ilaria Feresin, Agnese Faleschini, Michela Fontana, Giorgia Sirchia, Fabio Faletra, Flavio La Bianca, Martina Suergiu, Sarah Morgutti, Marcello Maschio, Massimo D'Adamo, Adamo Pio Raraigh, Karen S. Savoia, Anna Bottega, Roberta Mol Genet Genomic Med Clinical Reports BACKGROUND: Despite consolidated guidelines, the clinical diagnosis and prognosis of cystic fibrosis (CF) is still challenging mainly because of the extensive phenotypic heterogeneity and the high number of CFTR variants, including their combinations as complex alleles. RESULTS: We report a family with a complicated syndromic phenotype, which led to the suspicion not only of CF, but of a dominantly inherited skeletal dysplasia (SD). Whereas the molecular basis of the SD was not clarified, segregation analysis was central to make a correct molecular diagnosis of CF, as it allowed to identify three CFTR variants encompassing two known maternal mutations and a novel paternal microdeletion. CONCLUSION: This case well illustrates possible pitfalls in the clinical and molecular diagnosis of CF; presence of complex phenotypes deflecting clinicians from appropriate CF recognition, and/or identification of two mutations assumed to be in trans but with an unconfirmed status, which underline the importance of an in‐depth molecular CFTR analysis. John Wiley and Sons Inc. 2022-03-29 /pmc/articles/PMC9184661/ /pubmed/35348309 http://dx.doi.org/10.1002/mgg3.1926 Text en © 2022 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Clinical Reports Persico, Ilaria Feresin, Agnese Faleschini, Michela Fontana, Giorgia Sirchia, Fabio Faletra, Flavio La Bianca, Martina Suergiu, Sarah Morgutti, Marcello Maschio, Massimo D'Adamo, Adamo Pio Raraigh, Karen S. Savoia, Anna Bottega, Roberta Things come in threes: A new complex allele and a novel deletion within the CFTR gene complicate an accurate diagnosis of cystic fibrosis |
title | Things come in threes: A new complex allele and a novel deletion within the CFTR gene complicate an accurate diagnosis of cystic fibrosis |
title_full | Things come in threes: A new complex allele and a novel deletion within the CFTR gene complicate an accurate diagnosis of cystic fibrosis |
title_fullStr | Things come in threes: A new complex allele and a novel deletion within the CFTR gene complicate an accurate diagnosis of cystic fibrosis |
title_full_unstemmed | Things come in threes: A new complex allele and a novel deletion within the CFTR gene complicate an accurate diagnosis of cystic fibrosis |
title_short | Things come in threes: A new complex allele and a novel deletion within the CFTR gene complicate an accurate diagnosis of cystic fibrosis |
title_sort | things come in threes: a new complex allele and a novel deletion within the cftr gene complicate an accurate diagnosis of cystic fibrosis |
topic | Clinical Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9184661/ https://www.ncbi.nlm.nih.gov/pubmed/35348309 http://dx.doi.org/10.1002/mgg3.1926 |
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