{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:17:33Z","timestamp":1790702253801,"version":"4.1.0"},"reference-count":26,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T00:00:00Z","timestamp":1624406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008594","name":"European Hematology Association","doi-asserted-by":"publisher","award":["3978026"],"award-info":[{"award-number":["3978026"]}],"id":[{"id":"10.13039\/100008594","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007195","name":"Universit\u00e0 degli Studi di Napoli Federico II","doi-asserted-by":"publisher","award":["Bando Star Linea 1 - Junior Principal Investigator Grants - COINOR"],"award-info":[{"award-number":["Bando Star Linea 1 - Junior Principal Investigator Grants - COINOR"]}],"id":[{"id":"10.13039\/100007195","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Hereditary erythrocytes disorders include a large group of conditions with heterogeneous molecular bases and phenotypes. We analyzed here a case series of 155 consecutive patients with clinical suspicion of hereditary erythrocyte defects referred to the Medical Genetics Unit from 2018 to 2020. All of the cases followed a diagnostic workflow based on a targeted next-generation sequencing panel of 86 genes causative of hereditary red blood cell defects. We obtained an overall diagnostic yield of 84% of the tested patients. Monogenic inheritance was seen for 69% (107\/155), and multi-locus inheritance for 15% (23\/155). PIEZO1 and SPTA1 were the most mutated loci. Accordingly, 16\/23 patients with multi-locus inheritance showed dual molecular diagnosis of dehydrated hereditary stomatocytosis\/xerocytosis and hereditary spherocytosis. These dual inheritance cases were fully characterized and were clinically indistinguishable from patients with hereditary spherocytosis. Additionally, their ektacytometry curves highlighted alterations of dual inheritance patients compared to both dehydrated hereditary stomatocytosis and hereditary spherocytosis. Our findings expand the genotypic spectrum of red blood cell disorders and indicate that multi-locus inheritance should be considered for analysis and counseling of these patients. Of note, the genetic testing was crucial for diagnosis of patients with a complex mode of inheritance.<\/jats:p>","DOI":"10.3390\/genes12070958","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T21:14:51Z","timestamp":1624482891000},"page":"958","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Complex Modes of Inheritance in Hereditary Red Blood Cell Disorders: A Case Series Study of 155 Patients"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0493-812X","authenticated-orcid":false,"given":"Immacolata","family":"Andolfo","sequence":"first","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universit\u00e0 degli Studi di Napoli Federico II, 80131 Napoli, Italy"},{"name":"CEINGE Biotecnologie Avanzate, 80145 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Martone","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universit\u00e0 degli Studi di Napoli Federico II, 80131 Napoli, Italy"},{"name":"CEINGE Biotecnologie Avanzate, 80145 Naples, 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, 80131 Napoli, Italy"},{"name":"CEINGE Biotecnologie Avanzate, 80145 Naples, 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, 80131 Napoli, Italy"},{"name":"CEINGE Biotecnologie Avanzate, 80145 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Gambale","sequence":"additional","affiliation":[{"name":"CEINGE Biotecnologie Avanzate, 80145 Naples, Italy"},{"name":"Department of Laboratory Medicine (DAIMedLab), UOC Medical Genetics, \u2018Federico II\u2019 University Hospital, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Luca","family":"Forni","sequence":"additional","affiliation":[{"name":"Centro della Microcitemia e delle Anemie Congenite, Ospedale Galliera, 16128 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8375-6289","authenticated-orcid":false,"given":"Valeria","family":"Pinto","sequence":"additional","affiliation":[{"name":"Centro della Microcitemia e delle Anemie Congenite, Ospedale Galliera, 16128 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"G\u00f6ransson","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, The Queen Silvia Children\u2019s Hospital, Sahlgrenska University Hospital, 41345 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasiliki","family":"Papadopoulou","sequence":"additional","affiliation":[{"name":"Service and Central Laboratory of Haematology, Department of Oncology and Department of Laboratory Medicine and Pathology, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathilde","family":"Gavillet","sequence":"additional","affiliation":[{"name":"Service and Central Laboratory of Haematology, Department of Oncology and Department of Laboratory Medicine and Pathology, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2809-1552","authenticated-orcid":false,"given":"Mohsen","family":"Elalfy","sequence":"additional","affiliation":[{"name":"Thalassemia Centre, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Panarelli","sequence":"additional","affiliation":[{"name":"CEINGE Biotecnologie Avanzate, 80145 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3012-0356","authenticated-orcid":false,"given":"Giovanna","family":"Tomaiuolo","sequence":"additional","affiliation":[{"name":"CEINGE Biotecnologie Avanzate, 80145 Naples, Italy"},{"name":"Department of Chemical Engineering, Materials and Industrial Production, \u2018Federico II\u2019 University of Naples, 80125 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9558-0356","authenticated-orcid":false,"given":"Achille","family":"Iolascon","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universit\u00e0 degli Studi di Napoli Federico II, 80131 Napoli, Italy"},{"name":"CEINGE Biotecnologie Avanzate, 80145 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3624-7721","authenticated-orcid":false,"given":"Roberta","family":"Russo","sequence":"additional","affiliation":[{"name":"Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universit\u00e0 degli Studi di Napoli Federico II, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Da Costa, L., Narla, A., and 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