The First Report of a 290-bp Deletion in β-Globin  Gene in the South of Iran

Hamid, Mohammad; Nejad, Ladan Dawoody; Shariati, Gholamreza; Galehdari, Hamid; Saberi, Alihossein; Mohammadi-Anaei, Marziye

doi:10.18869/acadpub.ibj.21.2.126

Cited by 6 publications

(5 citation statements)

References 12 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: 57%

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: 57%

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: 81%

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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“…There are over 280 mutations that affect the β-globin gene, resulting in a phenotype of β-thalassemia; a vast majority are point mutations in certain regions of the beta-globin gene that are important in terms of function. 2 The clinical and laboratory findings are the basis for defining the three classifications of β-thalassemia: β-thalassemia minor, also referred to as carrier, is the heterozygous state that has no symptoms and manifests as mild anemia. Homozygosity or compound heterozygosity for β-thalassemia mutations result in more severe forms known as β-thalassemia intermedia and β-thalassemia major.…”

Section: Discussionmentioning

confidence: 99%

“…In the patients born with a 25% chance of being afflicted from parents who are healthy carriers, however, this condition is intermediate or severe. 1,2 Iran is one of the countries where β-thalassemia is prevalent among the Eastern Mediterranean countries. Regarding high consanguinity among the population, two and three million β-thalassemia carriers and 25 000 patients are estimated to exist in Iran.…”

Section: Introductionmentioning

confidence: 99%

Hb Narges Lab, a Novel Hemoglobin Variant of the β-Globin Gene

et al. 2022

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In this study, we describe a new missense variant on the β-globin gene in a heterozygous form in a female individual. Standard methods were used to determine red blood cell indices and perform hemoglobin analyses. Molecular studies were performed on the genomic DNA isolated from peripheral blood cells. Beta-globin genes were amplified and sequenced. We report a novel mutation on the β-globin gene (HBB), c.134 C>T; p.S44F variant, in the heterozygote state which was detected in a female of Persian ethnic origin in the Khuzestan province, southern Iran, that we named Hb Narges Lab (HbNL) variant. This mutation was predicted to be disease-causing in all except one in silico prediction tools. This variant was reported for the first time worldwide, had no shown hematological abnormalities but should be considered when inherited in the compound heterozygous form with β- thalassemia (β0-thal) carrier, which might result in the phenotype of thalassemia intermedia.

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The First Report of a 290-bp Deletion in β-Globin Gene in the South of Iran

Cited by 6 publications

References 12 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.

Hb Narges Lab, a Novel Hemoglobin Variant of the β-Globin Gene

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