Diagnostic approaches for inherited hemolytic anemia in the genetic era

Kim, Yonggoo; Park, Joonhong; Kim, Myungshin

doi:10.5045/br.2017.52.2.84

Cited by 45 publications

(53 citation statements)

References 98 publications

(109 reference statements)

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“…Previous studies have used different targeted NGS panels for the diagnosis of haemolytic anaemia on different platforms (Del Orbe Barreto et al , ; Kim et al , ). NGS is efficient and rapid for providing a correct diagnosis in clinical settings.…”

Section: Discussionmentioning

confidence: 99%

Deciphering molecular heterogeneity of Indian families with hereditary spherocytosis using targeted next‐generation sequencing: First South Asian study

et al. 2019

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Summary Defects in various erythrocyte membrane proteins genes (ankyrin, band‐3, β‐ and α‐spectrin and protein 4·2) can cause hereditary spherocytosis (HS). This molecular heterogeneity of HS, together with co‐inherited genetic modifiers, results in marked phenotypic variability among patients. We studied the molecular spectrum and genotype‐phenotype correlations in 73 families (with 113 patients) with HS. Deleterious variants including nonsense (42%), deletions (18%), splice site (20%), missense (10%) and duplication/insertion (10%) were found in 47 patients. The variants detected included sporadic and dominantly‐inherited defects in ANK1 (53·2%), SPTB (36·2%) and SLC4A1 (4·2%). Compound heterozygous variants in SPTA1 (6·4%) showed autosomal recessive inheritance. Alpha‐spectrin variants were associated with severe anaemia and splenectomy alleviated symptoms. Co‐inherited glucose‐6‐phosphate dehydrogenase (G6PD) deficiency was found in 15%. G6PD variants (n = 5) led to greater transfusion requirements (1‐8 times) in males with HS. Homozygosity (41%) for the promoter variant of UGT1A1 (Gilbert syndrome) led to a significantly higher mean bilirubin level (126·54 µmol/l) with a higher frequency of cholelithiasis (30%) (P < 0·001). This first‐ever south Asian study on the molecular spectrum of HS found ANK1 and SPTB genes variants to be the commonest with inheritance being sporadic/dominant. Next‐generation sequencing provided a relatively sensitive and rapid tool for molecular diagnosis with a diagnostic yield of 64·4%.

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Section: Discussionmentioning

confidence: 99%

Deciphering molecular heterogeneity of Indian families with hereditary spherocytosis using targeted next‐generation sequencing: First South Asian study

et al. 2019

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“…Our study is the biggest one with WES data in CHA patients. Regarding our results, exome sequencing in the field of CHA appears as highly performant, in HS but also in UH.Recommendations proposed by King et al in 2015[13], and compiled by Kim et al in 2017[64] concerning genetic testing for CHA diagnosis need to be updated, as they only recommended genetic testing in a limited number of cases as a second diagnostic step. A recent article of Rets et al in 2019 suggests that targeted NGS becomes the diagnosis standard tool in CHA molecular testing and that WES and WGS could represents the future[65].…”

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confidence: 63%

Exome sequencing for diagnosis of congenital hemolytic anemia

Mansour‐Hendili

Aissat

Badaoui

et al. 2020

Preprint

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Background: Congenital hemolytic anemia constitutes a heterogeneous group of rare genetic disorders of red blood cells. Diagnosis is based on clinical data, family history and phenotypic testing, genetic analyses being usually performed as a late step. In this study, we explored 40 patients with congenital hemolytic anemia by whole exome sequencing: 20 patients with hereditary spherocytosis and 20 patients with unexplained hemolysis.Results: A probable genetic cause of disease was identified in 82.5% of the patients (33/40): 100% of those with suspected hereditary spherocytosis (20/20) and 65% of those with unexplained hemolysis (13/20). We found that several patients carried genetic variations in more than one gene (3/20 in the hereditary spherocytosis group, 6/13 fully elucidated patients in the unexplained hemolysis group), giving a more accurate picture of the genetic complexity of congenital hemolytic anemia. In addition, whole exome sequencing allowed us to identify genetic variants in non-congenital hemolytic anemia genes that explained part of the phenotype in 3 patients.Conclusion: The rapid development of next generation sequencing has rendered the genetic study of these diseases much easier and cheaper. Whole exome sequencing use for congenital hemolytic anemia could provide a more precise and quicker diagnosis, improve patients’ healthcare and probably has to be democratized notably for complex cases.

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“…PK is encoded by the PKLR gene. This enzyme converts phosphoenolpyruvate to pyruvate, producing 50% of total ATP in RBC . The life span of these cells is dependent on the ATP produced in glycolysis.…”

Section: Resultsmentioning

confidence: 99%

Genetic variation influencing hemoglobin levels and risk for anemia across populations

Barrera-Reyes

Tejero

2019

Annals of the New York Academy of Sciences

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Hemoglobin (Hb) concentration is the outcome of the interaction between genetic variation and environmental factors, including nutritional status, sex, age, and altitude. Genetic diversity influencing this protein is complex and varies widely across populations. Variants related to abnormal Hb or altered characteristics of the erythrocytes increase the risk for anemia. The most prevalent are related to the inherited globin abnormalities affecting Hb production and structure. Malaria-endemic regions harbor the highest frequencies of variants associated with the most frequent monogenic diseases and the risk for nonnutritional anemia and are considered as public health problems. Variation in genes encoding for enzymes and membrane proteins in red blood cells also influence erythrocyte life span and risk for anemia. Most of these variants are rare. Interindividual variability of hematological parameters is also influenced by common genetic variation across the whole genome. Some of the identified variants are associated with Hb production, erythropoiesis, and iron metabolism. Specialized databases have been developed to organize and update the large body of available information on genetic variation related to Hb variation, their frequency, geographical distribution, and clinical significance. Our present review analyzed the underlying genetic factors that affect Hb concentrations, their clinical relevance, and geographical distribution across populations.

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Diagnostic approaches for inherited hemolytic anemia in the genetic era

Cited by 45 publications

References 98 publications

Deciphering molecular heterogeneity of Indian families with hereditary spherocytosis using targeted next‐generation sequencing: First South Asian study

Deciphering molecular heterogeneity of Indian families with hereditary spherocytosis using targeted next‐generation sequencing: First South Asian study

Exome sequencing for diagnosis of congenital hemolytic anemia

Genetic variation influencing hemoglobin levels and risk for anemia across populations

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