Please use this identifier to cite or link to this item:
https://repository.monashhealth.org/monashhealthjspui/handle/1/37000
Title: | Multi-gene panel testing improves diagnosis and management of patients with hereditary anemias. | Authors: | Forni G.L.;Caforio P.;Pinto V.;Pignataro P.;Radhakrishnan K. ;Unal S.;Tomaiuolo G.;Iolascon A.;Russo R.;Andolfo I.;Manna F.;Gambale A.;Marra R.;Rosato B.E. | Institution: | (Russo, Andolfo, Manna, Gambale, Marra, Rosato, Caforio, Iolascon) Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universita degli Studi di Napoli Federico II, Napoli, Italy (Russo, Andolfo, Manna, Gambale, Marra, Rosato, Caforio, Pignataro, Iolascon) CEINGE Biotecnologie Avanzate, Napoli, Italy (Pinto, Forni) Centro della Microcitemia e Anemie Congenite, Ospedale Galliera, Genova, Italy (Radhakrishnan) Paediatric Haematology/Oncology, Children's Cancer Centre, Monash Children's Hospital, Melbourne, VIC 3168, Australia (Radhakrishnan) Department of Haematology, Monash Medical Centre, Melbourne, VIC 3168, Australia (Unal) Division of Pediatric Hematology, Hacettepe University, Ankara, Turkey (Tomaiuolo) Dipartimento di Ingegneria Chimica, dei Materiali e della Prod. Indus., Federico II, Napoli, Italy | Issue Date: | 27-Apr-2018 | Copyright year: | 2018 | Publisher: | Wiley-Liss Inc. (E-mail: info@wiley.com) | Place of publication: | United States | Publication information: | American Journal of Hematology. 93 (5) (pp 672-682), 2018. Date of Publication: May 2018. | Journal: | American Journal of Hematology | Abstract: | 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-Blackfan 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-NGS panel, including 34 and 71 genes, respectively. Seventy-four 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-gene analysis modified the original clinical diagnosis in 45.8% of patients (nonmatched phenotype-genotype). 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 PKLR gene. Interestingly, we also identified a syndromic CDA patient with mild anemia and epilepsy, showing a homozygous mutation in CAD gene, recently associated to early infantile epileptic encephalopathy-50 and CDA-like anemia. Finally, we described a patient showing marked iron overload due to the coinheritance of PIEZO1 and SEC23B mutations, demonstrating that the multi-gene approach is valuable not only for achieving a correct and definitive diagnosis, but also for guiding treatment.Copyright © 2018 Wiley Periodicals, Inc. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1002/ajh.25058 | ORCID: | Russo, Roberta; ORCID: http://orcid.org/0000-0002-3624-7721 Andolfo, Immacolata; ORCID: http://orcid.org/0000-0003-0493-812X Forni, Gian Luca; ORCID: http://orcid.org/0000-0001-9833-1016 | Link to associated publication: | Click here for full text options | PubMed URL: | 29396846 [http://www.ncbi.nlm.nih.gov/pubmed/?term=29396846] | ISSN: | 0361-8609 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/37000 | Type: | Article | Subjects: | *hereditary anemia/di [Diagnosis] Blackfan Diamond anemia/di [Diagnosis] Blackfan Diamond anemia/et [Etiology] brain disease child clinical feature cohort analysis congenital dyserythropoietic anemia/cn [Congenital Disorder] congenital dyserythropoietic anemia/di [Diagnosis] controlled study diagnostic procedure diagnostic value disease association disease severity epilepsy family female gene gene mutation *genetic analysis *genetic disorder/cn [Congenital Disorder] *genetic disorder/di [Diagnosis] *genetic disorder/et [Etiology] genotype hemolytic anemia/cn [Congenital Disorder] hemolytic anemia/di [Diagnosis] hemolytic anemia/et [Etiology] hereditary spherocytosis/cn [Congenital Disorder] hereditary spherocytosis/di [Diagnosis] hereditary spherocytosis/et [Etiology] high throughput sequencing homozygote human infant inheritance iron overload/co [Complication] major clinical study male patient care phenotype preschool child priority journal school child stomatocytosis/cn [Congenital Disorder] stomatocytosis/di [Diagnosis] stomatocytosis/et [Etiology] genomic DNA/ec [Endogenous Compound] CAD gene *hereditary anemia/cn [Congenital Disorder] *hereditary anemia/et [Etiology] infantile epileptic encephalopathy piezo1 gene PKLR gene SEC23B gene adolescent *anemia/cn [Congenital Disorder] *anemia/di [Diagnosis] *anemia/et [Etiology] article Blackfan Diamond anemia/cn [Congenital Disorder] phenotype high throughput sequencing female hereditary spherocytosis / congenital disorder / diagnosis / etiology hemolytic anemia / congenital disorder / diagnosis / etiology genotype *genetic disorder / *congenital disorder / *diagnosis / *etiology *genetic analysis gene mutation gene adolescent *anemia / *congenital disorder / *diagnosis / *etiology Article Blackfan Diamond anemia / congenital disorder / diagnosis / etiology brain disease child clinical feature cohort analysis congenital dyserythropoietic anemia / congenital disorder / diagnosis controlled study diagnostic procedure diagnostic value disease association disease severity epilepsy family human infant inheritance iron overload / complication major clinical study male patient care homozygote preschool child priority journal school child stomatocytosis / congenital disorder / diagnosis / etiology |
Type of Clinical Study or Trial: | Observational study (cohort, case-control, cross sectional or survey) |
Appears in Collections: | Articles |
Show full item record
Items in Monash Health Research Repository are protected by copyright, with all rights reserved, unless otherwise indicated.