The use of <scp>next‐generation</scp> sequencing in the diagnosis of rare inherited anaemias: A Joint BSH/EHA Good Practice Paper*

Roy, Noémi; Costa, Lydie Da; Russo, Roberta; Bianchi, Paola; Mañú‐Pereira, María del Mar; Fermo, Elisa; Andolfo, Immacolata; Clark, Barnaby; Proven, Melanie; Sánchez, Mayka; Wijk, Richard van; Zwaag, Bert van der; Layton, Mark; Rees, David C.; Iolascon, Achille

doi:10.1111/bjh.18191

Cited by 7 publications

(12 citation statements)

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“…The British Society of Hematology and the European Hematology Association recently published a practice paper on the use of NGS for inherited anemias, including HHA, and recommended NGS after characterization of the phenotype, including gene panels for Diamond-Blackfan anemia, CDA, congenital sideroblastic anemia, RBC enzymopathy, and RBC membranopathy. 55 Patients suspected of a specific type of HHA achieved higher diagnostic yields than those with an unspecified HHA subtype. 73 However, in Korea, because of the widespread availability of t-NGS testing and limited access to tests characterizing the phenotype, such as RBC membrane analysis, ektacytometry, or RBC enzyme testing, molecular diagnosis is recommended as the initial step in the diagnostic workup, with phenotypic correlation performed later in the process.…”

Section: Diagnostic Hurdles and New Techniquesmentioning

confidence: 90%

“…As a result, many single-gene confirmatory tests that utilized Sanger sequencing have transitioned to NGS, particularly t-NGS for HHA. 45 53 54 55 Following these studies, cases with novel mutations have continued to be reported using Sanger sequencing, t-NGS, or whole-exome sequencing (WES). 56 57 58 59 60 …”

Section: Current Landscape Of Hha In Korea: Epidemiology Clinical Fea...mentioning

confidence: 99%

“… 65 66 67 Key parameters evaluated for differential diagnosis include the omin-value (the osmolality at which deformability reaches its minimum, similar to the 50% hemolysis point in a conventional OFT) and elongation index max (corresponding to the maximum deformability or elongation obtained near the isotonic osmolality). Although RBC ektacytometry is included in many diagnostic algorithms for RBC membranopathy, 55 64 it is not widely available for clinical use in Korea.…”

Section: Diagnostic Hurdles and New Techniquesmentioning

confidence: 99%

“…If necessary, valid ancillary assays should be performed to complement the analysis. 55 As copy number variations cannot be fully analyzed in some t-NGS panels, additional molecular testing is required in conjunction with t-NGS, especially for RBC hemoglobinopathy. Additionally, common variants detected in the population can be considered for the screening test.…”

Section: Diagnostic Hurdles and New Techniquesmentioning

confidence: 99%

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Current Status of Molecular Diagnosis of Hereditary Hemolytic Anemia in Korea

Chueh,

Shim,

Jung

et al. 2024

J Korean Med Sci

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Hereditary hemolytic anemia (HHA) is considered a group of rare hematological diseases in Korea, primarily because of its unique ethnic characteristics and diagnostic challenges. Recently, the prevalence of HHA has increased in Korea, reflecting the increasing number of international marriages and increased awareness of the disease. In particular, the diagnosis of red blood cell (RBC) enzymopathy experienced a resurgence, given the advances in diagnostic techniques. In 2007, the RBC Disorder Working Party of the Korean Society of Hematology developed the Korean Standard Operating Procedure for the Diagnosis of Hereditary Hemolytic Anemia, which has been continuously updated since then. The latest Korean clinical practice guidelines for diagnosing HHA recommends performing next-generation sequencing as a preliminary step before analyzing RBC membrane proteins and enzymes. Recent breakthroughs in molecular genetic testing methods, particularly next-generation sequencing, are proving critical in identifying and providing insight into cases of HHA with previously unknown diagnoses. These innovative molecular genetic testing methods have now become important tools for the management and care planning of patients with HHA. This review aims to provide a comprehensive overview of recent advances in molecular genetic testing for the diagnosis of HHA, with particular emphasis on the Korean context.

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Section: Diagnostic Hurdles and New Techniquesmentioning

confidence: 90%

Section: Current Landscape Of Hha In Korea: Epidemiology Clinical Fea...mentioning

confidence: 99%

Section: Diagnostic Hurdles and New Techniquesmentioning

confidence: 99%

Section: Diagnostic Hurdles and New Techniquesmentioning

confidence: 99%

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Current Status of Molecular Diagnosis of Hereditary Hemolytic Anemia in Korea

Chueh,

Shim,

Jung

et al. 2024

J Korean Med Sci

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“…Following the recommendations for diagnosis of HS and the more recent guidelines for the use of NGS in the diagnosis of rare inherited anaemias (Roy et al, 2022), in our study we limited the use of molecular investigations to 25 HS patients with atypical clinical presentation or intra-family variability, or patients who presented discrepancies between laboratory investigation and biochemical findings. Consequently, the results here reported Frontiers in Physiology frontiersin.org cannot be considered representative of the entire HS population referred to our Centre (Mariani et al, 2008;Vercellati et al, 2022), and could not be in line with the distribution of biochemical and molecular abnormalities reported in different patients cohorts (Chonat et al, 2019;van Vuren et al, 2019;Vives-Corrons et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Effect of primary lesions in cytoskeleton proteins on red cell membrane stability in patients with hereditary spherocytosis

et al. 2022

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We investigated by targeted next generation sequencing the genetic bases of hereditary spherocytosis in 25 patients and compared the molecular results with the biochemical lesion of RBC membrane obtained by SDS-PAGE analysis. The HS diagnosis was based on available guidelines for diagnosis of congenital hemolytic anemia, and patients were selected because of atypical clinical presentation or intra-family variability, or because presented discrepancies between laboratory investigation and biochemical findings. In all patients but 5 we identified pathogenic variants in SPTA1, SPTB, ANK1, SLC4A1, EPB42 genes able to justify the clinical phenotype. Interestingly, a correspondence between the biochemical lesion and the molecular defect was identified in only 11/25 cases, mostly with band 3 deficiency due to SLC4A1 mutations. Most of the mutations in SPTB and ANK1 gene didn’t hesitate in abnormalities of RBC membrane protein; conversely, in two cases the molecular lesion didn’t correspond to the biochemical defect, suggesting that a mutation in a specific cytoskeleton protein may result in a more complex RBC membrane damage or suffering. Finally, in two cases the HS diagnosis was maintained despite absence of both protein defect and molecular lesion, basing on clinical and family history, and on presence of clear laboratory markers of HS. The study revealed complex relationships between the primary molecular lesion and the final effect in the RBC membrane cytoskeleton, and further underlines the concept that there is not a unique approach to the diagnosis of HS.

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