{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:44:59Z","timestamp":1790905499832,"version":"4.1.0"},"reference-count":44,"publisher":"Elsevier BV","issue":"4","license":[{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,4,1]],"date-time":"2023-04-01T00:00:00Z","timestamp":1680307200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T00:00:00Z","timestamp":1672185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","jacionline.org","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Allergy and Clinical Immunology"],"published-print":{"date-parts":[[2023,4]]},"DOI":"10.1016\/j.jaci.2022.11.027","type":"journal-article","created":{"date-parts":[[2022,12,29]],"date-time":"2022-12-29T11:14:54Z","timestamp":1672312494000},"page":"1040-1049.e5","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":23,"title":["Insights into the pathogenesis of hereditary angioedema using genetic sequencing and recombinant protein expression analyses"],"prefix":"10.1016","volume":"151","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4933-0196","authenticated-orcid":false,"given":"Zhen","family":"Ren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuangxia","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiandao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H. James","family":"Wedner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Atkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jaci.2022.11.027_bib1","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1056\/NEJMcp0803977","article-title":"Clinical practice. Hereditary angioedema","volume":"359","author":"Zuraw","year":"2008","journal-title":"N Engl J Med"},{"key":"10.1016\/j.jaci.2022.11.027_bib2","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.jaci.2016.02.041","article-title":"Angioedema attacks in patients with hereditary angioedema: local manifestations of a systemic activation process","volume":"138","author":"Hofman","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2022.11.027_bib3","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1185\/03007995.2013.879441","article-title":"Hereditary angioedema: a brief review of new developments","volume":"30","author":"Altman","year":"2014","journal-title":"Curr Med Res Opin"},{"key":"10.1016\/j.jaci.2022.11.027_bib4","first-page":"164","article-title":"Molecular defects in hereditary angioneurotic edema","volume":"109","author":"Bissler","year":"1997","journal-title":"Proc Assoc Am Physicians"},{"key":"10.1016\/j.jaci.2022.11.027_bib5","series-title":"The complement factsbook","author":"Barnum","year":"2018"},{"key":"10.1016\/j.jaci.2022.11.027_bib6","doi-asserted-by":"crossref","DOI":"10.4061\/2011\/606797","article-title":"Serpin inhibition mechanism: a delicate balance between native metastable state and polymerization","volume":"2011","author":"Khan","year":"2011","journal-title":"J Amino Acids"},{"key":"10.1016\/j.jaci.2022.11.027_bib7","doi-asserted-by":"crossref","first-page":"2182","DOI":"10.1016\/j.str.2016.09.013","article-title":"How dextran sulfate affects C1-inhibitor activity: a model for polysaccharide potentiation","volume":"24","author":"Dijk","year":"2016","journal-title":"Structure"},{"key":"10.1016\/j.jaci.2022.11.027_bib8","doi-asserted-by":"crossref","first-page":"21100","DOI":"10.1074\/jbc.M700841200","article-title":"C1 inhibitor serpin domain structure reveals the likely mechanism of heparin potentiation and conformational disease","volume":"282","author":"Beinrohr","year":"2007","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jaci.2022.11.027_bib9","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S0140-6736(00)02483-1","article-title":"Hereditary angioedema with normal C1-inhibitor activity in women","volume":"356","author":"Bork","year":"2000","journal-title":"Lancet"},{"key":"10.1016\/j.jaci.2022.11.027_bib10","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.1432-1033.1991.tb15911.x","article-title":"Complete nucleotide sequence of the gene for human C1 inhibitor with an unusually high density of Alu elements","volume":"197","author":"Carter","year":"1991","journal-title":"Eur J Biochem"},{"key":"10.1016\/j.jaci.2022.11.027_bib11","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1111\/cei.12941","article-title":"Mutational spectrum of the SERPING1 gene in Swiss patients with hereditary angioedema","volume":"188","author":"Steiner","year":"2017","journal-title":"Clin Exp Immunol"},{"key":"10.1016\/j.jaci.2022.11.027_bib12","doi-asserted-by":"crossref","first-page":"4292","DOI":"10.1021\/bi00363a018","article-title":"Human C1 inhibitor: primary structure, cDNA cloning, and chromosomal localization","volume":"25","author":"Bock","year":"1986","journal-title":"Biochemistry"},{"key":"10.1016\/j.jaci.2022.11.027_bib13","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.gene.2018.10.084","article-title":"Gene mapping strategy for Alu elements rearrangements: detection of new large deletions in the SERPING1 gene causing hereditary angioedema in Brazilian families","volume":"685","author":"Nicolicht","year":"2019","journal-title":"Gene"},{"key":"10.1016\/j.jaci.2022.11.027_bib14","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1001\/archinte.161.20.2417","article-title":"Hereditary angioedema: a broad review for clinicians","volume":"161","author":"Nzeako","year":"2001","journal-title":"Arch Intern Med"},{"key":"10.1016\/j.jaci.2022.11.027_bib15","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0074043","article-title":"Ongoing contact activation in patients with hereditary angioedema","volume":"8","author":"Konings","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.jaci.2022.11.027_bib16","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1172\/JCI98869","article-title":"Dominant-negative SERPING1 variants cause intracellular retention of C1 inhibitor in hereditary angioedema","volume":"129","author":"Haslund","year":"2019","journal-title":"J Clin Invest"},{"key":"10.1016\/j.jaci.2022.11.027_bib17","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1038\/s41598-017-16667-w","article-title":"Intermittent C1-inhibitor deficiency associated with recessive inheritance: functional and structural insight","volume":"8","author":"Caccia","year":"2018","journal-title":"Sci Rep"},{"key":"10.1016\/j.jaci.2022.11.027_bib18","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.3390\/jcm10092023","article-title":"The genetics of hereditary angioedema: a review","volume":"10","author":"Santacroce","year":"2021","journal-title":"J Clin Med"},{"key":"10.1016\/j.jaci.2022.11.027_bib19","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1111\/all.15214","article-title":"The international WAO\/EAACI guideline for the management of hereditary angioedema\u2014the 2021 revision and update","volume":"77","author":"Maurer","year":"2022","journal-title":"Allergy"},{"key":"10.1016\/j.jaci.2022.11.027_bib20","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.3390\/cancers14081910","article-title":"Establishment of novel neuroendocrine carcinoma patient-derived xenograft models for receptor peptide-targeted therapy","volume":"14","author":"Tran","year":"2022","journal-title":"Cancers (Basel)"},{"key":"10.1016\/j.jaci.2022.11.027_bib21","article-title":"Clinicopathologic implications of complement genetic variants in kidney transplantation","volume":"8","author":"Ren","year":"2021","journal-title":"Front Med (Lausanne)"},{"key":"10.1016\/j.jaci.2022.11.027_bib22","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0243509","article-title":"Association of PARP1-specific polymorphisms and haplotypes with non-small cell lung cancer subtypes","volume":"15","author":"Jin","year":"2020","journal-title":"PLoS One"},{"key":"10.1016\/j.jaci.2022.11.027_bib23","doi-asserted-by":"crossref","first-page":"794","DOI":"10.3389\/fimmu.2020.00794","article-title":"Patterns of C1-inhibitor\/plasma serine protease complexes in healthy humans and in hereditary angioedema patients","volume":"11","author":"Kajdacsi","year":"2020","journal-title":"Front Immunol"},{"key":"10.1016\/j.jaci.2022.11.027_bib24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12016-021-08834-9","article-title":"In search of an association between genotype and phenotype in hereditary\u00a0angioedema due to C1-INH deficiency","volume":"61","author":"Loli-Ausejo","year":"2021","journal-title":"Clin Rev Allergy Immunol"},{"key":"10.1016\/j.jaci.2022.11.027_bib25","doi-asserted-by":"crossref","first-page":"6786","DOI":"10.1073\/pnas.87.17.6786","article-title":"Dysfunctional C1 inhibitor Ta: deletion of Lys-251 results in acquisition of an N-glycosylation site","volume":"87","author":"Parad","year":"1990","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.jaci.2022.11.027_bib26","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.jaci.2014.08.007","article-title":"Hereditary angioedema: molecular and clinical differences among European populations","volume":"135","author":"Speletas","year":"2015","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2022.11.027_bib27","doi-asserted-by":"crossref","DOI":"10.3389\/falgy.2022.836465","article-title":"Overview of SERPING1 variations identified in Hungarian patients with hereditary angioedema","volume":"3","author":"Szabo","year":"2022","journal-title":"Front Allergy"},{"key":"10.1016\/j.jaci.2022.11.027_bib28","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1002\/humu.20197","article-title":"Hereditary angioedema: the mutation spectrum of SERPING1\/C1NH in a large Spanish cohort","volume":"26","author":"Roche","year":"2005","journal-title":"Hum Mutat"},{"key":"10.1016\/j.jaci.2022.11.027_bib29","doi-asserted-by":"crossref","first-page":"5619","DOI":"10.1038\/s41598-021-85094-9","article-title":"Post translational modifications of milk proteins in geographically diverse goat breeds","volume":"11","author":"Rout","year":"2021","journal-title":"Sci Rep"},{"key":"10.1016\/j.jaci.2022.11.027_bib30","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1002\/humu.23917","article-title":"SERPING1 mutation update: mutation spectrum and C1 inhibitor phenotypes","volume":"41","author":"Ponard","year":"2020","journal-title":"Hum Mutat"},{"key":"10.1016\/j.jaci.2022.11.027_bib31","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1016\/j.jaci.2007.02.012","article-title":"Treatment of acute edema attacks in hereditary angioedema with a bradykinin receptor-2 antagonist (icatibant)","volume":"119","author":"Bork","year":"2007","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2022.11.027_bib32","article-title":"Peptides based on the reactive center loop of Manduca sexta serpin-3 block its protease inhibitory function","volume":"10","author":"Li","year":"2020","journal-title":"Sci Rep"},{"key":"10.1016\/j.jaci.2022.11.027_bib33","doi-asserted-by":"crossref","first-page":"25","DOI":"10.3389\/fmed.2019.00025","article-title":"SERPINs\u2014from trap to treatment","volume":"6","author":"Sanrattana","year":"2019","journal-title":"Front Med (Lausanne)"},{"key":"10.1016\/j.jaci.2022.11.027_bib34","doi-asserted-by":"crossref","first-page":"e241","DOI":"10.1371\/journal.pcbi.0030241","article-title":"Stereochemical criteria for prediction of the effects of proline mutations on protein stability","volume":"3","author":"Bajaj","year":"2007","journal-title":"PLoS Comput Biol"},{"key":"10.1016\/j.jaci.2022.11.027_bib35","doi-asserted-by":"crossref","first-page":"7650","DOI":"10.1021\/bi00081a008","article-title":"Effects of mutations in the hinge region of serpins","volume":"32","author":"Hopkins","year":"1993","journal-title":"Biochemistry"},{"key":"10.1016\/j.jaci.2022.11.027_bib36","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1007\/s12016-016-8543-x","article-title":"Genetics of hereditary angioedema revisited","volume":"51","author":"Germenis","year":"2016","journal-title":"Clin Rev Allergy Immunol"},{"key":"10.1016\/j.jaci.2022.11.027_bib37","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1067\/mai.2000.110471","article-title":"Frequent de novo mutations and exon deletions in the C1inhibitor gene of patients with angioedema","volume":"106","author":"Pappalardo","year":"2000","journal-title":"J Allergy Clin Immunol"},{"key":"10.1016\/j.jaci.2022.11.027_bib38","doi-asserted-by":"crossref","first-page":"18088","DOI":"10.1016\/S0021-9258(17)46815-3","article-title":"A\u00a0hinge\u00a0region mutation in C1-inhibitor (Ala436\u2192Thr) results in nonsubstrate-like behavior and in polymerization of the molecule","volume":"268","author":"Aulak","year":"1993","journal-title":"J Biol Chem"},{"key":"10.1016\/j.jaci.2022.11.027_bib39","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1074\/mcp.RA117.000240","article-title":"N- and O-glycosylation analysis of human C1-inhibitor reveals extensive mucin-type O-glycosylation","volume":"17","author":"Stavenhagen","year":"2018","journal-title":"Mol Cell Proteomics"},{"key":"10.1016\/j.jaci.2022.11.027_bib40","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1078\/0171-2985-00151","article-title":"Structural and functional aspects of C1-inhibitor","volume":"205","author":"Bos","year":"2002","journal-title":"Immunobiology"},{"key":"10.1016\/j.jaci.2022.11.027_bib41","doi-asserted-by":"crossref","DOI":"10.3389\/falgy.2022.860355","article-title":"Diagnosing pediatric patients with hereditary C1-inhibitor deficiency\u2014experience from the Hungarian angioedema center of reference and excellence","volume":"3","author":"Andrasi","year":"2022","journal-title":"Front Allergy"},{"key":"10.1016\/j.jaci.2022.11.027_bib42","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1710-1492-6-18","article-title":"Pediatric hereditary angioedema due to C1-inhibitor deficiency","volume":"6","author":"Farkas","year":"2010","journal-title":"Allergy Asthma Clin Immunol"},{"key":"10.1016\/j.jaci.2022.11.027_bib43","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1160\/TH04-01-0008","article-title":"Inhibition of plasma kallikrein by C1-inhibitor: role of endothelial cells and the amino-terminal domain of C1-inhibitor","volume":"92","author":"Ravindran","year":"2004","journal-title":"Thromb Haemost"},{"key":"10.1016\/j.jaci.2022.11.027_bib44","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.gene.2018.05.029","article-title":"Targeted next-generation sequencing for the molecular diagnosis of hereditary angioedema due to C1-inhibitor deficiency","volume":"667","author":"Loules","year":"2018","journal-title":"Gene"}],"container-title":["Journal of Allergy and Clinical Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S009167492202557X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S009167492202557X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T09:41:22Z","timestamp":1758793282000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S009167492202557X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4]]},"references-count":44,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["S009167492202557X"],"URL":"https:\/\/doi.org\/10.1016\/j.jaci.2022.11.027","relation":{},"ISSN":["0091-6749"],"issn-type":[{"value":"0091-6749","type":"print"}],"subject":[],"published":{"date-parts":[[2023,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Insights into the pathogenesis of hereditary angioedema using genetic sequencing and recombinant protein expression analyses","name":"articletitle","label":"Article Title"},{"value":"Journal of Allergy and Clinical Immunology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jaci.2022.11.027","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.","name":"copyright","label":"Copyright"}]}}