The 12.6 kb-deletion in the  -globin gene cluster is the known Thai/Vietnamese (  )0-thalassemia commonly found in Southeast Asia

Chalaow, Nipon; Thein, Swee Lay; Viprakasit, Vip

doi:10.3324/haematol.2013.090613

Cited by 6 publications

(3 citation statements)

References 9 publications

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“…We found more deletions in individuals with high HbF than those with low HbF levels indicating their role in HbF synthesis pathways. A number of significant deletions have been reported before, particularly in the globin cluster [60][61][62]. In this study, we have identified additional potential deletions across the targeted regions ( Table 2).…”

Section: Discussionmentioning

confidence: 60%

Identifying genetic variants and pathways associated with extreme levels of fetal hemoglobin in sickle cell disease in Tanzania

et al. 2020

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Background: Sickle cell disease (SCD) is a blood disorder caused by a point mutation on the beta globin gene resulting in the synthesis of abnormal hemoglobin. Fetal hemoglobin (HbF) reduces disease severity, but the levels vary from one individual to another. Most research has focused on common genetic variants which differ across populations and hence do not fully account for HbF variation. Methods: We investigated rare and common genetic variants that influence HbF levels in 14 SCD patients to elucidate variants and pathways in SCD patients with extreme HbF levels (≥7.7% for high HbF) and (≤2.5% for low HbF) in Tanzania. We performed targeted next generation sequencing (Illumina_Miseq) covering exonic and other significant fetal hemoglobin-associated loci, including BCL11A, MYB, HOXA9, HBB, HBG1, HBG2, CHD4, KLF1, MBD3, ZBTB7A and PGLYRP1. Results: Results revealed a range of genetic variants, including bi-allelic and multi-allelic SNPs, frameshift insertions and deletions, some of which have functional importance. Notably, there were significantly more deletions in individuals with high HbF levels (11% vs 0.9%). We identified frameshift deletions in individuals with high HbF levels and frameshift insertions in individuals with low HbF. CHD4 and MBD3 genes, interacting in the same sub-network, were identified to have a significant number of pathogenic or non-synonymous mutations in individuals with low HbF levels, suggesting an important role of epigenetic pathways in the regulation of HbF synthesis. Conclusions: This study provides new insights in selecting essential variants and identifying potential biological pathways associated with extreme HbF levels in SCD interrogating multiple genomic variants associated with HbF in SCD.

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Section: Discussionmentioning

confidence: 60%

Identifying genetic variants and pathways associated with extreme levels of fetal hemoglobin in sickle cell disease in Tanzania

et al. 2020

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show abstract

“…We found more deletions in individuals with high HbF than those with low HbF levels indicating their role in HbF synthesis pathways. A number of signi cant deletions have been reported before, particularly in the globin cluster [60,61,62]. In this study, we have identi ed additional potential deletions across the targeted regions ( Table 2).…”

Section: Discussionmentioning

confidence: 83%

Identifying genetic variants and pathways associated with extreme levels of fetal hemoglobin in Sickle Cell Disease in Tanzania.

Nkya

Mwita

Mgaya

et al. 2020

Preprint

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Background: Sickle cell disease (SCD) is a blood disorder caused by a point mutation on the beta globin gene resulting in the synthesis of abnormal hemoglobin. Fetal hemoglobin (HbF) reduces disease severity, but the levels vary from one individual to another. Most research has focused on common variants which differ across populations and hence do not fully account for HbF variation. Methods: We investigated rare and common genetic variants that influence HbF levels in 14 SCD patients to elucidate variants and pathways in SCD patients with extreme HbF levels (≥7.7% for high HbF) and (≤2.5% for low HbF) in Tanzania. We performed targeted next generation sequencing (Illumina_Miseq) covering exonic and other significant fetal hemoglobin-associated loci, including BCL11A, MYB, HOXA9, HBB, HBG1, HBG2, CHD4, KLF1, MBD3, ZBTB7A and PGLYRP1.Results: Results revealed a range of genetic variants, including bi-allelic and multi-allelic SNPs, frameshift insertions and deletions, some of which have functional importance. Notably, there were significantly more deletions in individuals with high HbF levels (11% vs 0.9%). We identified deletions with high HbF levels and frameshift insertions in individuals with low HbF. CHD4 and MBD3 genes, interacting in the same sub-network, were identified to have a significant number of pathogenic or non-synonymous mutations in individuals with low HbF levels, suggesting an important role of epigenetic pathways in the regulation of HbF synthesis. Conclusions: This study provides new insights in selecting essential variants and identifying potential biological pathways associated with extreme HbF levels in SCD using multiple genomic variants associated with HbF in SCD.

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“…We read with interest the letter by Chalaow et al 1 concerning 12.6 kb-deletion in the beta(b)-globin gene cluster known as the Thai/Vietnamese (db) 0 -thalassemia commonly found in Southeast Asia. The main purpose of our study 2 was not to report the discovery of new deletions but to focus on the impact of the loss of a regulatory element in the increase in fetal hemoglobin (HbF) by using short deletions.…”

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confidence: 95%

Low fetal hemoglobin rates in patients carrying Thai ( )0-deletion and Turkish ( )0-deletion/inversion strengthen the hypothesis that the 5' BCL11A binding site plays a major role in its fetal hemoglobin inhibitory regulation. Response to "The 12.6 kb-deletion in the -globin gene cluster is the known Thai/Vietnamese ( )0-thalassemia commonly found in Southeast Asia"

Ghedira

Pissard²

2013

Haematologica

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Low fetal hemoglobin rates in patients carryingWe read with interest the letter by Chalaow et al.1 concerning 12.6 kb-deletion in the beta(b)-globin gene cluster known as the Thai/Vietnamese (db) 0 -thalassemia commonly found in Southeast Asia. The main purpose of our study 2 was not to report the discovery of new deletions but to focus on the impact of the loss of a regulatory element in the increase in fetal hemoglobin (HbF) by using short deletions. From the deletions described in our work, the 12610 pb del was claimed to be reported for the first time. However, it appears that this deletion was actually described under various names and referenced as: i) Thai (db) 7 Clearly, we had not sufficiently searched the GenBank or compared our results with these data.Thus, it would be more appropriate to report that, in a patient from India, we had identified a deletion known as being likely to be present more frequently in South-East Asian populations (Thailand, Laos and Vietnam). The lack of a standardized and exhaustive database of the known bglobin locus deletions is one reason for the mistake in identifying a known deletion as a new discovery. Moreover, since deletion mapping was performed in mid-2011, the breakpoint sequence loaded on the GenBank browser was not identified as being that of a previously known deletion. So, we propose to submit this deletion to the HbVAr database, with a table summarizing its main features, and including all the publications that have described this event with a unified co-ordinate. We will carry out this submission using the table presented here ( Table 1) that summarizes the main features of patients described in these publications.Interestingly, when we look at the phenotypes reported in these publications, we find that the fetal hemoglobin (HbF) rates are very close to those reported in our data (

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The 12.6 kb-deletion in the -globin gene cluster is the known Thai/Vietnamese ( )0-thalassemia commonly found in Southeast Asia

Cited by 6 publications

References 9 publications

Identifying genetic variants and pathways associated with extreme levels of fetal hemoglobin in sickle cell disease in Tanzania

Identifying genetic variants and pathways associated with extreme levels of fetal hemoglobin in sickle cell disease in Tanzania

Identifying genetic variants and pathways associated with extreme levels of fetal hemoglobin in Sickle Cell Disease in Tanzania.

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