Genotype-first analysis of a generally healthy population cohort supports genetic testing for diagnosis of hereditary angioedema of unknown cause
Abstract Background Hereditary angioedema (HAE) is a potentially life-threatening group of conditions that is often underdiagnosed or misdiagnosed. As HAE is typically diagnosed by detecting C1 inhibitor deficiency, there is a critical need for methods that can identify affected individuals with nor...
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doaj-29d4a023fb1444d28f7ac8f81b3c77392020-11-25T03:27:20ZengBMCAllergy, Asthma & Clinical Immunology1710-14922019-05-011511410.1186/s13223-019-0346-1Genotype-first analysis of a generally healthy population cohort supports genetic testing for diagnosis of hereditary angioedema of unknown causeDale L. Bodian0Thierry Vilboux1Natalie S. Hauser2Inova Translational Medicine Institute, Inova Health SystemInova Translational Medicine Institute, Inova Health SystemInova Translational Medicine Institute, Inova Health SystemAbstract Background Hereditary angioedema (HAE) is a potentially life-threatening group of conditions that is often underdiagnosed or misdiagnosed. As HAE is typically diagnosed by detecting C1 inhibitor deficiency, there is a critical need for methods that can identify affected individuals with normal C1 inhibitor. The recent discovery of associations between PLG K330E and ANGPT1 A119S and HAE of unknown genetic cause (HAE-U), has raised the possibility that genetic evaluation could be used to diagnose HAE-U in patients with unexplained angioedema or non-confirmatory laboratory testing. Case presentation We analyzed genome sequences from a generally healthy population cohort of 2820 adults and identified PLG K330E in one individual. Subsequent review of this participant’s medical history revealed symptoms clinically attributed to allergy of unknown etiology but that are consistent with published descriptions of HAE patients carrying the PLG K330E variant. The participant, a 31 year old female, reported lip and tongue angioedema, without wheals, which did not respond to treatment with steroids or antihistamines. Conclusions The genotype-first approach demonstrated that detection of PLG K330E in undiagnosed or misdiagnosed individuals can identify patients actually affected with HAE-U. The genetic diagnosis will facilitate selection of appropriate treatment, discontinuation of therapies ineffective for this condition, and timely diagnosis of affected family members. The results support a role of PLG K330E in the pathogenesis of HAE and suggest that genetic testing be considered as an approach to diagnose patients with unexplained angioedema.http://link.springer.com/article/10.1186/s13223-019-0346-1Nextgen sequencingClinical sequencingHereditary angioedemaAngioedemaPlasminogenPLG |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dale L. Bodian Thierry Vilboux Natalie S. Hauser |
spellingShingle |
Dale L. Bodian Thierry Vilboux Natalie S. Hauser Genotype-first analysis of a generally healthy population cohort supports genetic testing for diagnosis of hereditary angioedema of unknown cause Allergy, Asthma & Clinical Immunology Nextgen sequencing Clinical sequencing Hereditary angioedema Angioedema Plasminogen PLG |
author_facet |
Dale L. Bodian Thierry Vilboux Natalie S. Hauser |
author_sort |
Dale L. Bodian |
title |
Genotype-first analysis of a generally healthy population cohort supports genetic testing for diagnosis of hereditary angioedema of unknown cause |
title_short |
Genotype-first analysis of a generally healthy population cohort supports genetic testing for diagnosis of hereditary angioedema of unknown cause |
title_full |
Genotype-first analysis of a generally healthy population cohort supports genetic testing for diagnosis of hereditary angioedema of unknown cause |
title_fullStr |
Genotype-first analysis of a generally healthy population cohort supports genetic testing for diagnosis of hereditary angioedema of unknown cause |
title_full_unstemmed |
Genotype-first analysis of a generally healthy population cohort supports genetic testing for diagnosis of hereditary angioedema of unknown cause |
title_sort |
genotype-first analysis of a generally healthy population cohort supports genetic testing for diagnosis of hereditary angioedema of unknown cause |
publisher |
BMC |
series |
Allergy, Asthma & Clinical Immunology |
issn |
1710-1492 |
publishDate |
2019-05-01 |
description |
Abstract Background Hereditary angioedema (HAE) is a potentially life-threatening group of conditions that is often underdiagnosed or misdiagnosed. As HAE is typically diagnosed by detecting C1 inhibitor deficiency, there is a critical need for methods that can identify affected individuals with normal C1 inhibitor. The recent discovery of associations between PLG K330E and ANGPT1 A119S and HAE of unknown genetic cause (HAE-U), has raised the possibility that genetic evaluation could be used to diagnose HAE-U in patients with unexplained angioedema or non-confirmatory laboratory testing. Case presentation We analyzed genome sequences from a generally healthy population cohort of 2820 adults and identified PLG K330E in one individual. Subsequent review of this participant’s medical history revealed symptoms clinically attributed to allergy of unknown etiology but that are consistent with published descriptions of HAE patients carrying the PLG K330E variant. The participant, a 31 year old female, reported lip and tongue angioedema, without wheals, which did not respond to treatment with steroids or antihistamines. Conclusions The genotype-first approach demonstrated that detection of PLG K330E in undiagnosed or misdiagnosed individuals can identify patients actually affected with HAE-U. The genetic diagnosis will facilitate selection of appropriate treatment, discontinuation of therapies ineffective for this condition, and timely diagnosis of affected family members. The results support a role of PLG K330E in the pathogenesis of HAE and suggest that genetic testing be considered as an approach to diagnose patients with unexplained angioedema. |
topic |
Nextgen sequencing Clinical sequencing Hereditary angioedema Angioedema Plasminogen PLG |
url |
http://link.springer.com/article/10.1186/s13223-019-0346-1 |
work_keys_str_mv |
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