{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T15:26:35Z","timestamp":1778253995046,"version":"3.51.4"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,5,2]],"date-time":"2020-05-02T00:00:00Z","timestamp":1588377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81700115"],"award-info":[{"award-number":["81700115"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81803562"],"award-info":[{"award-number":["81803562"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J Lab Hematology"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Paroxysmal Nocturnal Hemoglobinuria (PNH) is an acquired clonal disease of hematopoietic stem cells. It is caused by somatic mutation of the X\u2010linked<jats:italic>PIGA<\/jats:italic>gene, resulting in a deficient expression of glycosylphosphatidylinositol\u2010anchored proteins (GPI\u2010APs). In this study, we aimed to explore the diagnostic value of next\u2010generation sequencing (NGS) and potential molecular basis in PNH patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Genomic DNA of 85 PNH patients was analyzed by a 114\u2010gene NGS panel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mutational analysis of<jats:italic>PIGA<\/jats:italic>identified 124 mutations in 92% PNH patients, including 101 distinct mutations and 23 recurrent mutations. Among them, 102 mutations were newly reported. Most mutations were located in exon 2 of<jats:italic>PIGA<\/jats:italic>gene, and truncated mutation was the most common one. Other mutations were detected in 26 out of 85 cases, including five cases of<jats:italic>DNMT3A<\/jats:italic>variants, four cases of<jats:italic>ASXL1<\/jats:italic>variants, and four cases of<jats:italic>U2AF1<\/jats:italic>variants. Clonal analysis was performed in one case and outlined a linear evolution pattern in classic PNH. There was a positive correlation between number of<jats:italic>PIGA<\/jats:italic>mutations and fraction of GPI\u2010APs deficient granulocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The detection of<jats:italic>PIGA<\/jats:italic>mutations and additional variants by targeted NGS not only shed light on the genetic characteristics of PNH, but also provided an important reference value in the diagnosis of PNH at molecular level.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ijlh.13228","type":"journal-article","created":{"date-parts":[[2020,5,2]],"date-time":"2020-05-02T12:29:00Z","timestamp":1588422540000},"page":"473-481","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Identification of acquired<i>PIGA<\/i>mutations and additional variants by next\u2010generation sequencing in paroxysmal nocturnal hemoglobinuria"],"prefix":"10.1111","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0008-3427","authenticated-orcid":false,"given":"Jing","family":"Li","sequence":"first","affiliation":[{"name":"SINO\u2010US Diagnostics Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yani","family":"Lin","sequence":"additional","affiliation":[{"name":"SINO\u2010US Diagnostics Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long","family":"Chen","sequence":"additional","affiliation":[{"name":"SINO\u2010US Diagnostics Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Qin","sequence":"additional","affiliation":[{"name":"SINO\u2010US Diagnostics Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Tan","sequence":"additional","affiliation":[{"name":"SINO\u2010US Diagnostics Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junyan","family":"Zou","sequence":"additional","affiliation":[{"name":"SINO\u2010US Diagnostics Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donglei","family":"Zhang","sequence":"additional","affiliation":[{"name":"SINO\u2010US Diagnostics Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanbo","family":"Nie","sequence":"additional","affiliation":[{"name":"SINO\u2010US Diagnostics Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangjuan","family":"Wang","sequence":"additional","affiliation":[{"name":"SINO\u2010US Diagnostics Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"SINO\u2010US Diagnostics Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enbin","family":"Liu","sequence":"additional","affiliation":[{"name":"SINO\u2010US Diagnostics Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuejing","family":"Chen","sequence":"additional","affiliation":[{"name":"SINO\u2010US Diagnostics Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun","family":"Ru","sequence":"additional","affiliation":[{"name":"SINO\u2010US Diagnostics Tianjin China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,5,2]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.28"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1040-8428(99)00052-9"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/asheducation-2008.1.104"},{"issue":"2","key":"e_1_2_8_5_1","first-page":"19","article-title":"Pesg PNH diagnosis, follow\u2010up and treatment guidelines","volume":"6","author":"Sahin F","year":"2016","journal-title":"Am J Blood Res"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0320(20000815)42:4<234::AID-CYTO3>3.0.CO;2-6"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0320(20000815)42:4<223::AID-CYTO2>3.0.CO;2-D"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.12619"},{"issue":"4","key":"e_1_2_8_9_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/cyto.b.20525","article-title":"Guidelines for the diagnosis and monitoring of paroxysmal nocturnal hemoglobinuria and related disorders by flow cytometry","volume":"78","author":"Borowitz MJ","year":"2010","journal-title":"Cytometry B Clin Cytom"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.2001.03191.x"},{"issue":"4","key":"e_1_2_8_11_1","first-page":"255","article-title":"Paroxysmal nocturnal hemoglobinuria: insights from recent advances in molecular biology","volume":"15","author":"Bessler M","year":"2001","journal-title":"Transfus Med Rev"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02982015"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI74747"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802749105"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-05-574889"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2018.03.002"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V126.23.4546.4546"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V83.9.2418.2418"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.2.646"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-04-1717"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2017.01.004"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1754"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14790"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cancergen.2015.01.007"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0138-5"},{"issue":"17","key":"e_1_2_8_27_1","first-page":"1674","article-title":"Somatic mutations and clonal hematopoiesis in aplastic anemia","volume":"373","author":"Mufti GJ","year":"2015","journal-title":"N Engl J Med"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3343\/alm.2019.39.5.438"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3415"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.028"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10166"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90250-T"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.274"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.9.5209"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2013.869802"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1106968"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI77984"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.35.4894"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1311084"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2009.01338.x"}],"container-title":["International Journal of Laboratory Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fijlh.13228","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ijlh.13228","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ijlh.13228","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ijlh.13228","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T02:37:18Z","timestamp":1722825438000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ijlh.13228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,2]]},"references-count":39,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1111\/ijlh.13228"],"URL":"https:\/\/doi.org\/10.1111\/ijlh.13228","archive":["Portico"],"relation":{},"ISSN":["1751-5521","1751-553X"],"issn-type":[{"value":"1751-5521","type":"print"},{"value":"1751-553X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,2]]},"assertion":[{"value":"2020-02-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}