Complex Modes of Inheritance in Hereditary Red Blood Cell Disorders: A Case Series Study of 155 Patients
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 o...
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| Format: | Article |
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MDPI AG
2021-06-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/12/7/958 |
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| author | Immacolata Andolfo Stefania Martone Barbara Eleni Rosato Roberta Marra Antonella Gambale Gian Luca Forni Valeria Pinto Magnus Göransson Vasiliki Papadopoulou Mathilde Gavillet Mohsen Elalfy Antonella Panarelli Giovanna Tomaiuolo Achille Iolascon Roberta Russo |
| author_facet | Immacolata Andolfo Stefania Martone Barbara Eleni Rosato Roberta Marra Antonella Gambale Gian Luca Forni Valeria Pinto Magnus Göransson Vasiliki Papadopoulou Mathilde Gavillet Mohsen Elalfy Antonella Panarelli Giovanna Tomaiuolo Achille Iolascon Roberta Russo |
| author_sort | Immacolata Andolfo |
| collection | DOAJ |
| description | 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). <i>PIEZO1</i> and <i>SPTA1</i> 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. |
| first_indexed | 2024-03-10T10:06:38Z |
| format | Article |
| id | doaj.art-7b2fa893de2e40f497d0bb485cbd0294 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-10T10:06:38Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-7b2fa893de2e40f497d0bb485cbd02942023-11-22T01:28:28ZengMDPI AGGenes2073-44252021-06-0112795810.3390/genes12070958Complex Modes of Inheritance in Hereditary Red Blood Cell Disorders: A Case Series Study of 155 PatientsImmacolata Andolfo0Stefania Martone1Barbara Eleni Rosato2Roberta Marra3Antonella Gambale4Gian Luca Forni5Valeria Pinto6Magnus Göransson7Vasiliki Papadopoulou8Mathilde Gavillet9Mohsen Elalfy10Antonella Panarelli11Giovanna Tomaiuolo12Achille Iolascon13Roberta Russo14Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, 80131 Napoli, ItalyDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, 80131 Napoli, ItalyDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, 80131 Napoli, ItalyDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, 80131 Napoli, ItalyCEINGE Biotecnologie Avanzate, 80145 Naples, ItalyCentro della Microcitemia e delle Anemie Congenite, Ospedale Galliera, 16128 Genoa, ItalyCentro della Microcitemia e delle Anemie Congenite, Ospedale Galliera, 16128 Genoa, ItalyDepartment of Paediatrics, The Queen Silvia Children’s Hospital, Sahlgrenska University Hospital, 41345 Gothenburg, SwedenService and Central Laboratory of Haematology, Department of Oncology and Department of Laboratory Medicine and Pathology, Lausanne University Hospital (CHUV), 1011 Lausanne, SwitzerlandService and Central Laboratory of Haematology, Department of Oncology and Department of Laboratory Medicine and Pathology, Lausanne University Hospital (CHUV), 1011 Lausanne, SwitzerlandThalassemia Centre, Faculty of Medicine, Ain Shams University, Cairo 11566, EgyptCEINGE Biotecnologie Avanzate, 80145 Naples, ItalyCEINGE Biotecnologie Avanzate, 80145 Naples, ItalyDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, 80131 Napoli, ItalyDipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, 80131 Napoli, ItalyHereditary 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). <i>PIEZO1</i> and <i>SPTA1</i> 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.https://www.mdpi.com/2073-4425/12/7/958red blood cell defectstargeted next-generation sequencingmulti-locus inheritance<i>PIEZO1</i><i>SPTA1</i> |
| spellingShingle | Immacolata Andolfo Stefania Martone Barbara Eleni Rosato Roberta Marra Antonella Gambale Gian Luca Forni Valeria Pinto Magnus Göransson Vasiliki Papadopoulou Mathilde Gavillet Mohsen Elalfy Antonella Panarelli Giovanna Tomaiuolo Achille Iolascon Roberta Russo Complex Modes of Inheritance in Hereditary Red Blood Cell Disorders: A Case Series Study of 155 Patients Genes red blood cell defects targeted next-generation sequencing multi-locus inheritance <i>PIEZO1</i> <i>SPTA1</i> |
| title | Complex Modes of Inheritance in Hereditary Red Blood Cell Disorders: A Case Series Study of 155 Patients |
| title_full | Complex Modes of Inheritance in Hereditary Red Blood Cell Disorders: A Case Series Study of 155 Patients |
| title_fullStr | Complex Modes of Inheritance in Hereditary Red Blood Cell Disorders: A Case Series Study of 155 Patients |
| title_full_unstemmed | Complex Modes of Inheritance in Hereditary Red Blood Cell Disorders: A Case Series Study of 155 Patients |
| title_short | Complex Modes of Inheritance in Hereditary Red Blood Cell Disorders: A Case Series Study of 155 Patients |
| title_sort | complex modes of inheritance in hereditary red blood cell disorders a case series study of 155 patients |
| topic | red blood cell defects targeted next-generation sequencing multi-locus inheritance <i>PIEZO1</i> <i>SPTA1</i> |
| url | https://www.mdpi.com/2073-4425/12/7/958 |
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