Molecular diagnostic update in hereditary hemolytic anemia and neonatal hyperbilirubinemia

Rets, Anton; Clayton, Adam L.; Christensen, Robert D.; Agarwal, Archana

doi:10.1111/ijlh.13014

Cited by 40 publications

(31 citation statements)

References 47 publications

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“…Recommendations proposed by King et al in 2015 [13], and compiled by Kim et al in 2017 [74] concerning the indications of genetic testing for CHA diagnosis need to be updated, as they only recommended genetic testing in a limited number of cases and 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 [75]. Our results show that molecular diagnosis with WES could easily be democratized and be of great help to understand patients' phenotype, adapting therapeutic approach (such as splenectomy) and to allow genetic counseling.…”

Section: Discussionmentioning

confidence: 58%

Exome sequencing for diagnosis of congenital hemolytic anemia

Mansour‐Hendili

Aissat

Badaoui

et al. 2020

Orphanet J Rare Dis

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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 in 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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Section: Discussionmentioning

confidence: 58%

Exome sequencing for diagnosis of congenital hemolytic anemia

Mansour‐Hendili

Aissat

Badaoui

et al. 2020

Orphanet J Rare Dis

View full text Add to dashboard Cite

show abstract

“…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]. Our results show that molecular diagnosis with WES could easily be democratized and is fundamental for understanding patients' phenotype, adapting therapeutic approach (such as splenectomy) and permiting genetic counseling.…”

mentioning

confidence: 59%

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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“…The functional tests are therefore crucial to assess the pathogenicity of new variants detected by NGS. Moreover, further problems can arise from the need for adequate coverage of the genes when there are copy number variants and GC−rich regions with low−complexity (Rets et al, 2019). Currently, a targeted-NGS approach is preferred in the diagnostic work-up for these disorders (Agarwal et al, 2016;Del Orbe Barreto et al, 2016;Niss et al, 2016;Roy et al, 2016;Russo et al, 2018;Choi et al, 2019;Kedar et al, 2019;Svidnicki et al, 2020).…”

Section: Second-generation Sequencing: Ngs Short Readsmentioning

confidence: 99%

Genetics and Genomics Approaches for Diagnosis and Research Into Hereditary Anemias

et al. 2020

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The hereditary anemias are a relatively heterogeneous set of disorders that can show wide clinical and genetic heterogeneity, which often hampers correct clinical diagnosis. The classical diagnostic workflow for these conditions generally used to start with analysis of the family and personal histories, followed by biochemical and morphological evaluations, and ending with genetic testing. However, the diagnostic framework has changed more recently, and genetic testing is now a suitable approach for differential diagnosis of these patients. There are several approaches to this genetic testing, the choice of which depends on phenotyping, genetic heterogeneity, and gene size. For patients who show complete phenotyping, single-gene testing remains recommended. However, genetic analysis now includes next-generation sequencing, which is generally based on custom-designed targeting panels and whole-exome sequencing. The use of next-generation sequencing also allows the identification of new causative genes, and of polygenic conditions and genetic factors that modify disease severity of hereditary anemias. In the research field, whole-genome sequencing is useful for the identification of non-coding causative mutations, which might account for the disruption of transcriptional factor occupancy sites and cis-regulatory elements. Moreover, advances in high-throughput sequencing techniques have now resulted in the identification of genome-wide profiling of the chromatin structures known as the topologically associating domains. These represent a recurrent disease mechanism that exposes genes to inappropriate regulatory elements, causing errors in gene expression. This review focuses on the challenges of diagnosis and research into hereditary anemias, with indications of both the advantages and disadvantages. Finally, we consider the future perspectives for the use of next-generation sequencing technologies in this era of precision medicine.

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Molecular diagnostic update in hereditary hemolytic anemia and neonatal hyperbilirubinemia

Cited by 40 publications

References 47 publications

Exome sequencing for diagnosis of congenital hemolytic anemia

Exome sequencing for diagnosis of congenital hemolytic anemia

Exome sequencing for diagnosis of congenital hemolytic anemia

Genetics and Genomics Approaches for Diagnosis and Research Into Hereditary Anemias

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