{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T14:35:52Z","timestamp":1782484552055,"version":"3.54.5"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T00:00:00Z","timestamp":1762300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Hereditary Angioedema (HAE) due to C1-esterase inhibitor (C1-INH) deficiency or dysfunction (C1-INH-HAE), is an autosomal dominant genetic disease characterized by recurrent cutaneous and submucosal swelling episodes most often caused by heterozygous pathogenic Single Nucleotide Variants (SNVs), small insertions or deletions (indels) or Copy Number Variants (CNVs) in the\n                    <jats:italic>SERPING1<\/jats:italic>\n                    gene, coding for C1-INH. Rare subtypes of HAE not associated with\n                    <jats:italic>SERPING1<\/jats:italic>\n                    pathogenic variants (nC1-INH-HAE) have been described. This case report aimed to characterize a 55-year-old proband, without a family history of hereditary diseases, presenting with a clinical diagnosis of C1-INH-HAE, primary Sj\u00f6gren syndrome, and unexplained neuropathic symptoms. Firstly, targeted Next-Generation Sequencing and Multiple Ligation-dependent Probe Amplification (MLPA) were performed on the proband\u2019s genomic DNA to analyze the\n                    <jats:italic>SERPING1<\/jats:italic>\n                    gene. Secondly, Chromosomal Microarray Analysis (CMA) and Fluorescence In Situ Hybridization analysis were performed to confirm the cytogenomics results. MLPA detected a heterozygous variant corresponding to the whole\n                    <jats:italic>SERPING1<\/jats:italic>\n                    gene deletion on chromosome 11, a very rare cause of C1-INH-HAE. CMA defined breakpoints and disclosed an additional pathogenic CNV on chromosome 17, involving\n                    <jats:italic>PMP22<\/jats:italic>\n                    gene, and causing Neuropathy, Hereditary, With Liability To Pressure Palsies disease. The clinical consequences of\n                    <jats:italic>SERPING1<\/jats:italic>\n                    and\n                    <jats:italic>PMP22<\/jats:italic>\n                    haploinsufficiency are associated with the unusual constellation of clinical symptoms, unraveling an unexpected cytogenomics architecture with two co-occurring disease-causing CNVs in a previously genetically undiagnosed patient.\n                  <\/jats:p>","DOI":"10.1186\/s13023-025-04092-6","type":"journal-article","created":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T10:45:48Z","timestamp":1762339548000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Unexpected genomic architecture in a sporadic case of C1-INH Hereditary Angioedema: the hidden heritability"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0341-6461","authenticated-orcid":false,"given":"Enrica","family":"Marchionni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Mannucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Di Tommaso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Nardone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Albanese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Novelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica Carla","family":"Sangiuolo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Triggianese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Novelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,5]]},"reference":[{"key":"4092_CR1","doi-asserted-by":"publisher","unstructured":"Mannucci L, Shkodrani B, Triggianese P, Marchionni E, Bergamini A, Novelli G. Hereditary angioedema: from gene to gene therapy, eLS. 2024;3:1\u20138. https:\/\/doi.org\/10.1002\/9780470015902.a0029764.","DOI":"10.1002\/9780470015902.a0029764"},{"issue":"1","key":"4092_CR2","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1002\/humu.23917","volume":"41","author":"D Ponard","year":"2020","unstructured":"Ponard D, Gaboriaud C, Charignon D, Ghannam A, Wagenaar-Bos IGA, Roem D, et al. SERPING1 mutation update: mutation spectrum and C1 inhibitor phenotypes. Hum Mutat 2020, Jan;41(1):38\u201357. https:\/\/doi.org\/10.1002\/humu.23917.","journal-title":"Hum. Mutat"},{"issue":"6","key":"4092_CR3","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1002\/humu.22981","volume":"37","author":"DD Jt","year":"2016","unstructured":"den Dunnen JT, Dalgleish R, Maglott DR, Hart RK, Greenblatt MS, McGowan-Jordan J, et al. HGVS recommendations for the description of sequence variants: 2016 update. Hum Mutat 2016, Jun;37(6):564\u201369. https:\/\/doi.org\/10.1002\/humu.22981.","journal-title":"Hum. Mutat"},{"issue":"5","key":"4092_CR4","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American college of medical genetics and Genomics and the association for molecular pathology. Genet Med. 2015, May;17(5):405\u201324. https:\/\/doi.org\/10.1038\/gim.2015.30.","journal-title":"Genet Med"},{"key":"4092_CR5","doi-asserted-by":"publisher","unstructured":"Riggs ER, Andersen EF, Cherry AM, Kantarci S, Kearney H, Patel A, et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American college of medical genetics and Genomics (ACMG) and the clinical genome resource (ClinGen). Genet Med. 2020, Feb;22(2):245\u201357. Epub 2019 Nov 6.Erratum in: Genet Med. 2021 Nov; 23(11):2230. doi 10.1038\/s41436-021-01150-9. https:\/\/doi.org\/10.1038\/s41436-019-0686-8.","DOI":"10.1038\/s41436-019-0686-8"},{"issue":"7","key":"4092_CR6","doi-asserted-by":"publisher","first-page":"1961","DOI":"10.1111\/all.15214","volume":"77","author":"M Maurer","year":"2022","unstructured":"Maurer M, Magerl M, Betschel S, Aberer W, Ansotegui IJ, Ayg\u00f6ren-P\u00fcrs\u00fcn E, et al. The international WAO\/EAACI guideline for the management of hereditary angioedema-the 2021 revision and update. Allergy. 2022, Jul;77(7):1961\u201390. https:\/\/doi.org\/10.1111\/all.15214.","journal-title":"Allergy"},{"issue":"1","key":"4092_CR7","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1080\/14712598.2024.2441845","volume":"25","author":"G Costanzo","year":"2025","unstructured":"Costanzo G, Sambugaro G, Sartorio S, Zanichelli A, Firinu D. New drugs for the treatment of hereditary angioedema. Expert Opin Biol Ther. 2025, Jan;25(1):79\u201391. https:\/\/doi.org\/10.1080\/14712598.2024.2441845.","journal-title":"Expert Opin Biol Ther"},{"issue":"1","key":"4092_CR8","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s13023-025-03562-1","volume":"20","author":"R Lochbaum","year":"2025","unstructured":"Lochbaum R, Hoffmann TK, Greve J, Hahn J. Analysis of prodromal symptoms and need for short-term prophylaxis in angioedema patients under long-term prophylaxis. 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Patient was collected in a path that belongs to common clinical practice.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Patient involved in the study signed an informed consent for publication accordingly to ethical guidelines.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publication"}},{"value":"The authors declare no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interest"}}],"article-number":"562"}}