Prevalence of CFTR variants in primary immunodeficiency patients with bronchiectasis is an important modifying cofactor
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved..
BACKGROUND: Cystic fibrosis (CF) is one of the most common life-limiting autosomal-recessive disorders and is caused by genetic defects in the CF transmembrane conductance regulator (CFTR) gene. Some of the features of this multisystem disease can be present in primary immunodeficiency (PID).
OBJECTIVE: We hypothesized that a carrier CFTR status might be associated with worse outcome regarding structural lung disease in patients with PID.
METHODS: A within-cohort and population-level statistical genomic analysis of a large European cohort of PID patients was performed using genome sequence data. Genomic analysis of variant pathogenicity was performed.
RESULTS: Compared to the general population, p.Phe508del carriage was enriched in lung-related PID. Additionally, carriage of several pathogenic CFTR gene variants were increased in PID associated with structural lung damage compared to PID patients without the structural lung damage. We identified 3 additional biallelic cases, including several variants not traditionally considered to cause CF.
CONCLUSION: Genome sequencing identified cases of CFTR dysfunction in PID, driving an increased susceptibility to infection. Large national genomic services provide an opportunity for precision medicine by interpreting subtle features of genomic diversity when treating traditional Mendelian disorders.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:152 |
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| Enthalten in: |
The Journal of allergy and clinical immunology - 152(2023), 1 vom: 29. Juli, Seite 257-265 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lawless, Dylan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.07.2023 Date Revised 30.01.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.jaci.2023.01.035 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM353342777 |
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| 245 | 1 | 0 | |a Prevalence of CFTR variants in primary immunodeficiency patients with bronchiectasis is an important modifying cofactor |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 10.07.2023 | ||
| 500 | |a Date Revised 30.01.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: Cystic fibrosis (CF) is one of the most common life-limiting autosomal-recessive disorders and is caused by genetic defects in the CF transmembrane conductance regulator (CFTR) gene. Some of the features of this multisystem disease can be present in primary immunodeficiency (PID) | ||
| 520 | |a OBJECTIVE: We hypothesized that a carrier CFTR status might be associated with worse outcome regarding structural lung disease in patients with PID | ||
| 520 | |a METHODS: A within-cohort and population-level statistical genomic analysis of a large European cohort of PID patients was performed using genome sequence data. Genomic analysis of variant pathogenicity was performed | ||
| 520 | |a RESULTS: Compared to the general population, p.Phe508del carriage was enriched in lung-related PID. Additionally, carriage of several pathogenic CFTR gene variants were increased in PID associated with structural lung damage compared to PID patients without the structural lung damage. We identified 3 additional biallelic cases, including several variants not traditionally considered to cause CF | ||
| 520 | |a CONCLUSION: Genome sequencing identified cases of CFTR dysfunction in PID, driving an increased susceptibility to infection. Large national genomic services provide an opportunity for precision medicine by interpreting subtle features of genomic diversity when treating traditional Mendelian disorders | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Bronchiectasis | |
| 650 | 4 | |a CFTR | |
| 650 | 4 | |a cystic fibrosis | |
| 650 | 4 | |a genomics | |
| 650 | 4 | |a primary immunodeficiency | |
| 650 | 7 | |a Cystic Fibrosis Transmembrane Conductance Regulator |2 NLM | |
| 650 | 7 | |a 126880-72-6 |2 NLM | |
| 650 | 7 | |a CFTR protein, human |2 NLM | |
| 700 | 1 | |a Allen, Hana Lango |e verfasserin |4 aut | |
| 700 | 1 | |a Thaventhiran, James E D |e verfasserin |4 aut | |
| 700 | 1 | |a Goddard, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Burren, Oliver S |e verfasserin |4 aut | |
| 700 | 1 | |a Robson, Evie |e verfasserin |4 aut | |
| 700 | 0 | |a NIHR BioResource–Rare Diseases Consortium |e verfasserin |4 aut | |
| 700 | 1 | |a Peckham, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Smith, Kenneth G C |e verfasserin |4 aut | |
| 700 | 1 | |a Savic, Sinisa |e verfasserin |4 aut | |
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