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Exome sequencing for diagnosis of congenital hemolytic anemia
Lamisse MANSOUR-HENDILI
Assistance Publique - Hopitaux de Paris
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7887-9156
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Orphanet Journal of Rare Diseases.
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. .
Keywords
hemolysis, red blood cell, membrane, NGS, anemia, congenital, mutation
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CURRENT STATUS: Published
Version 2
Posted 19 May, 2020
Published
On 08 Jul, 2020
No community comments so far
Editorial decision: Accept
On 27 May, 2020
Review #2 received
Received 19 May, 2020
Review #1 received
Received 19 May, 2020
Reviewer #1 agreed
On 11 May, 2020
Reviewer #2 agreed
On 11 May, 2020
Reviewers invited
Invitations sent on 08 May, 2020
Editor assigned
On 07 May, 2020
Submission checks complete
On 06 May, 2020
Editor invited
On 06 May, 2020
No comments provided
Editorial decision: Major revision
On 09 Apr, 2020
Review #2 received
Received 23 Mar, 2020
Review #1 received
Received 15 Mar, 2020
Reviewer #2 agreed
On 09 Mar, 2020
Reviewers invited
Invitations sent on 26 Feb, 2020
Reviewer #1 agreed
On 26 Feb, 2020
Editor assigned
On 21 Feb, 2020
First submitted
On 20 Feb, 2020
Submission checks complete
On 20 Feb, 2020
Editor invited
On 20 Feb, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Hematology
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This preprint is under consideration at Orphanet Journal of Rare Diseases. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Exome sequencing for diagnosis of congenital hemolytic anemia
Lamisse MANSOUR-HENDILI
Assistance Publique - Hopitaux de Paris
Corresponding Author
ORCiD: https://orcid.org/0000-0001-7887-9156
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
Version 2
Posted 19 May, 2020
Published
On 08 Jul, 2020
No community comments so far
Editorial decision: Accept
On 27 May, 2020
Review #2 received
Received 19 May, 2020
Review #1 received
Received 19 May, 2020
Reviewer #1 agreed
On 11 May, 2020
Reviewer #2 agreed
On 11 May, 2020
Reviewers invited
Invitations sent on 08 May, 2020
Editor assigned
On 07 May, 2020
Submission checks complete
On 06 May, 2020
Editor invited
On 06 May, 2020
No comments provided
Editorial decision: Major revision
On 09 Apr, 2020
Review #2 received
Received 23 Mar, 2020
Review #1 received
Received 15 Mar, 2020
Reviewer #2 agreed
On 09 Mar, 2020
Reviewers invited
Invitations sent on 26 Feb, 2020
Reviewer #1 agreed
On 26 Feb, 2020
Editor assigned
On 21 Feb, 2020
First submitted
On 20 Feb, 2020
Submission checks complete
On 20 Feb, 2020
Editor invited
On 20 Feb, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Hematology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published version at Orphanet Journal of Rare Diseases.
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. .
Figure 1
Figure 2
Figure 3