{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:25:00Z","timestamp":1790713500163,"version":"4.1.0"},"reference-count":28,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,2,24]],"date-time":"2018-02-24T00:00:00Z","timestamp":1519430400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003852","name":"Regione Campania","doi-asserted-by":"publisher","award":["DGRC2362\/07"],"award-info":[{"award-number":["DGRC2362\/07"]}],"id":[{"id":"10.13039\/501100003852","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J Hematol"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations in more than 70 genes cause hereditary anemias (HA), a highly heterogeneous group of rare\/low frequency disorders in which we included: hyporegenerative anemias, as congenital dyserythropoietic anemia (CDA) and Diamond\u2010Blackfan anemia; hemolytic anemias due to erythrocyte membrane defects, as hereditary spherocytosis and stomatocytosis; hemolytic anemias due to enzymatic defects. The study describes the diagnostic workflow for HA, based on the development of two consecutive versions of a targeted\u2010NGS panel, including 34 and 71 genes, respectively. Seventy\u2010four probands from 62 unrelated families were investigated. Our study includes the most comprehensive gene set for these anemias and the largest cohort of patients described so far. We obtained an overall diagnostic yield of 64.9%. Despite 54.2% of cases showed conclusive diagnosis fitting well to the clinical suspicion, the multi\u2010gene analysis modified the original clinical diagnosis in 45.8% of patients (nonmatched phenotype\u2010genotype). Of note, 81.8% of nonmatched patients were clinically suspected to suffer from CDA. Particularly, 45.5% of the probands originally classified as CDA exhibited a conclusive diagnosis of chronic anemia due to enzymatic defects, mainly due to mutations in <jats:italic>PKLR<\/jats:italic> gene. Interestingly, we also identified a syndromic CDA patient with mild anemia and epilepsy, showing a homozygous mutation in <jats:italic>CAD<\/jats:italic> gene, recently associated to early infantile epileptic encephalopathy\u201050 and CDA\u2010like anemia. Finally, we described a patient showing marked iron overload due to the coinheritance of <jats:italic>PIEZO1<\/jats:italic> and <jats:italic>SEC23B<\/jats:italic> mutations, demonstrating that the multi\u2010gene approach is valuable not only for achieving a correct and definitive diagnosis, but also for guiding treatment.<\/jats:p>","DOI":"10.1002\/ajh.25058","type":"journal-article","created":{"date-parts":[[2018,2,3]],"date-time":"2018-02-03T08:12:48Z","timestamp":1517645568000},"page":"672-682","source":"Crossref","is-referenced-by-count":140,"title":["Multi\u2010gene panel testing improves diagnosis and management of patients with hereditary anemias"],"prefix":"10.1002","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3624-7721","authenticated-orcid":false,"given":"Roberta","family":"Russo","sequence":"first","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche Universit\u00e0 degli Studi di Napoli Federico II Napoli Italy"},{"name":"CEINGE Biotecnologie Avanzate Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0493-812X","authenticated-orcid":false,"given":"Immacolata","family":"Andolfo","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche Universit\u00e0 degli Studi di Napoli Federico II Napoli Italy"},{"name":"CEINGE Biotecnologie Avanzate Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Manna","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche Universit\u00e0 degli Studi di Napoli Federico II Napoli Italy"},{"name":"CEINGE Biotecnologie Avanzate Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Gambale","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche Universit\u00e0 degli Studi di Napoli Federico II Napoli Italy"},{"name":"CEINGE Biotecnologie Avanzate Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Marra","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche Universit\u00e0 degli Studi di Napoli Federico II Napoli Italy"},{"name":"CEINGE Biotecnologie Avanzate Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara Eleni","family":"Rosato","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche Universit\u00e0 degli Studi di Napoli Federico II Napoli Italy"},{"name":"CEINGE Biotecnologie Avanzate Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Caforio","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche Universit\u00e0 degli Studi di Napoli Federico II Napoli Italy"},{"name":"CEINGE Biotecnologie Avanzate Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Pinto","sequence":"additional","affiliation":[{"name":"Centro della Microcitemia e Anemie Congenite, Ospedale Galliera Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piero","family":"Pignataro","sequence":"additional","affiliation":[{"name":"CEINGE Biotecnologie Avanzate Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kottayam","family":"Radhakrishnan","sequence":"additional","affiliation":[{"name":"Paediatric Haematology\/Oncology, Children's Cancer Centre, Monash Children's Hospital Melbourne Victoria 3168 Australia"},{"name":"Department of Haematology Monash Medical Centre Melbourne Victoria 3168 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sule","family":"Unal","sequence":"additional","affiliation":[{"name":"Division of Pediatric Hematology Hacettepe University Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Tomaiuolo","sequence":"additional","affiliation":[{"name":"Dipartimento di Ingegneria Chimica dei Materiali e della Prod. Indus., Federico II Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9833-1016","authenticated-orcid":false,"given":"Gian Luca","family":"Forni","sequence":"additional","affiliation":[{"name":"Centro della Microcitemia e Anemie Congenite, Ospedale Galliera Genova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Achille","family":"Iolascon","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche Universit\u00e0 degli Studi di Napoli Federico II Napoli Italy"},{"name":"CEINGE Biotecnologie Avanzate Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,2,24]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1586\/17474086.2016.1131608"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2017.10.017"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.142463"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24929"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.hoc.2015.11.006"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2015.12.009"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14221"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijlh.12551"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.14131"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21866"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24853"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3703"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2013.02.003"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-016-2716-9"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2017.04.003"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI78619"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature15247"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.01.046"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-008-0294-y"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-11-753525"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv057"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww300"},{"key":"e_1_2_8_25_1","article-title":"PIEZO1\u2010R1864H rare variant accounts for a genetic phenotype\u2010modifier role in dehydrated hereditary stomatocytosis","author":"Andolfo I","year":"2017","journal-title":"Haematologica."},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.142372"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-06-724328"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1521754113"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2016.162966"}],"container-title":["American Journal of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajh.25058","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajh.25058","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T04:05:58Z","timestamp":1694318758000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajh.25058"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,24]]},"references-count":28,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["10.1002\/ajh.25058"],"URL":"https:\/\/doi.org\/10.1002\/ajh.25058","archive":["Portico"],"relation":{},"ISSN":["0361-8609","1096-8652"],"issn-type":[{"value":"0361-8609","type":"print"},{"value":"1096-8652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,24]]}}}