Alpha thalassemia deletions found in suspected cases of beta thalassemia major in Pakistani population

Shahid, Saba; Nadeem, Mohammad; Zahid, Danish; Hassan, Jawad; Ansari, Saqib Hussain; Shamsi, Tahir

doi:10.12669/pjms.332.11834

Cited by 8 publications

(5 citation statements)

References 20 publications

(14 reference statements)

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“…The fact that our patients with triplication and quadruplication of the α-globin gene and mono-allelic HBB mutations had a moderate-to-severe thalassemia intermedia phenotype was consistent with the literature. Our study findings similarly supported reports that α/β globin ratios influence the severity of the disease [17,22,36]. In Family 1, the mother's heterozygous HBB mutation and HBA gene deletion/ quadruplication in trans form resulted in a milder phenotype than the index.…”

Section: Discussionsupporting

confidence: 92%

“…In addition to moderate/mild homozygous variations, compound heterozygotes or an elevated fetal hemoglobin level can influence the clinical picture [13][14][15]. Co-existing α-thalassemia and β-thalassemia is most frequently reported in Asian countries, which have a high prevalence of carriers of both αand β-thalassemia [16][17][18][19].…”

Section: Association Between Hba Locus Copy Number Gains and Pathogenic Hbb Gene Variantsmentioning

confidence: 99%

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Association of HBA gene copy number gains with pathogenic HBB gene variants

Karakaş¹

2021

Int J Med Biochem

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8]. Four alleles of 2 structurally similar genes, HBA1 and HBA2 are responsible for α-globin gene expression and are critically important when establishing genotype-phenotype relationships in patients with β-thalassemia. Although the HBA1 gene Objectives: Alpha (α) and beta (β) thalassemia are the most prevalent genetic hematological disorders. The co-occurrence of silent β-thalassemia with excess α-globin gene copies is associated with the thalassemia intermedia phenotype. This study was an investigation of the α-globulin gene dosage and sequence variations in thalassemia patients. Methods: Multiplex ligation-dependent probe amplification and Sanger sequencing were used to identify the hemoglobin subunit alpha 1 (HBA1) and HBA2 gene alterations in 32 patients. Deletion, duplication, and other findings were analyzed in the index cases and family members. Results: Four of the 32 cases (12.5%) were found to have gross duplications. Two cases demonstrated α-globin triplication, and 2 had a quadruplicated HBA1/2 genes. Affected family members revealed genotype-phenotype correlation. In 1 patient, it was observed that quadruplicated HBA genes co-occurrence with hemoglobin subunit beta (HBB) mutation was inherited from his mother. Notably, the mother did not demonstrate any thalassemia phenotype. Further investigation showed that the mother was carrying a single copy HBA gene deletion in the trans allele that explained her clinical condition. Conclusion:This study examined the effect of increased copies of the HBA gene in HBB gene pathogenic variant carriers. The results indicated that β-thalassemia mutations with a co-occurrence of increased α-globin gene dosage is not very rare condition. Patients with clinical findings incompatible with their HBB genotypes should be investigated for small and gross α-globin gene variants in order to provide genetic counseling and prenatal diagnosis follow-up, as appropriate.

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Section: Discussionsupporting

confidence: 92%

Section: Association Between Hba Locus Copy Number Gains and Pathogenic Hbb Gene Variantsmentioning

confidence: 99%

Association of HBA gene copy number gains with pathogenic HBB gene variants

Karakaş¹

2021

Int J Med Biochem

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“…Reticulocyte count was observed on days +14, +21, and +28 to determine early transplant rejection. The Glucksberg-Seattle criteria [ 16 ] were used to classify acute GVHD, which was evaluated within the first 100 days of transplantation.…”

Section: Methodsmentioning

confidence: 99%

The Impact of ABO Incompatibility on the Outcomes of Hematopoietic Stem Cell Transplantation: A Single-Center Study From Pakistan

Borhany,

Ali,

Ghias

et al. 2023

Cureus

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Background and objective Allogeneic hematopoietic stem cell transplantation (alloHSCT) provides curative treatment for several hematological illnesses. In this study, we evaluated the impact of ABO compatibility and incompatibility on outcomes and complications related to hematopoietic stem cell transplantation (HSCT) performed for various hematological disorders at our center. Methodology This was a retrospective, single-center, cohort study in which patients were categorized according to the ABO match and mismatch status. The mismatch group was further subcategorized into major, minor, and bidirectional groups. Results A total of 117 patients underwent alloHSCT, out of which 82 (70.1%) were male and 35 (30%) were female. The median age of the patients was 9.5 years (range: 46 years). The most common indications for stem cell transplant were beta-thalassemia major (BTM; n=58, 49%) and aplastic anemia (AA; n=42, 35.8%). However, the outcomes in match and mismatch groups showed significant results for positive direct Coombs test (DCT), indicating the occurrence of hemolysis. Despite the increased need for blood transfusions, ABO blood group incompatibility (ABOi) had no negative impact on the clinical results. Conclusion Based on our findings, ABO incompatibility does not affect the outcomes in patients undergoing alloHSCT. Patient monitoring can aid in early detection and treatment, thereby minimizing the frequency of fatal events.

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“…18 The inherited disorders in children including the lysosomal storage disorder in Pakistan need to be focused for molecular studies and the trend has been increasing as it will provide child health care. [22][23][24][25]…”

Section: G>a Mutationmentioning

confidence: 99%

Mutational spectrum of SMPD1 gene in Pakistani Niemann-Pick disease patients

Cheema¹,

Rasool

Anjum³

et al. 2020

Pak J Med Sci

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Objective: Genetic variation analysis of rare autosomal recessive Niemann-Pick disease (NPD) Pakistani patients. Methods: We sequenced the SMPD1 gene including its all coding and flanking regions in seven unrelated sporadic patients suffering from Niemann-Pick disease through targeted exome sequencing. Genetic variants mapping and their protein predictions were evaluated using different bioinformatics tools and clinical phenotypes were correlated. The study was conducted from January 2018 to March 2019 at The Children’s Hospital Lahore. Results: We have mapped five different mutations in SMPD1 gene of enrolled patients with a novel homozygous missense variant (c.1718G>C) (p.Trp573Ser) in one patient. A missense mutation (c.1267C>T) (p.His423Tyr) has been identified in three unrelated patients. A nonsense mutation (c.1327C>T) (p.Arg443Term) and one missense mutation (c.1493G>A) (p.Arg498His) mapped in one patient each. A compound heterozygous mutation has been mapped in one patient (c.740G>A) (p.Gly247Asp); (c.1493G>A) (p.Arg498His). Pathogenic effect of novel variant has been predicted through in-silico analysis and has not been reported in general overall population in the globe. Conclusion: This is the first report of genetic demographic assessment of Niemann-Pick disease in Pakistan. The mapped mutations would be helpful to build a disease variants algorithm of Pakistani population. This will be used for determining disease clinical magnitude along with provision of genetic screening services in affected families. doi: https://doi.org/10.12669/pjms.36.3.467 How to cite this:Cheema HA, Rasool IG, Anjum MN, Zahoor MY. Mutational spectrum of SMPD1 gene in Pakistani Niemann-Pick disease patients. Pak J Med Sci. 2020;36(3):---------. doi: https://doi.org/10.12669/pjms.36.3.467 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Alpha thalassemia deletions found in suspected cases of beta thalassemia major in Pakistani population

Cited by 8 publications

References 20 publications

Association of HBA gene copy number gains with pathogenic HBB gene variants

Association of HBA gene copy number gains with pathogenic HBB gene variants

The Impact of ABO Incompatibility on the Outcomes of Hematopoietic Stem Cell Transplantation: A Single-Center Study From Pakistan

Mutational spectrum of SMPD1 gene in Pakistani Niemann-Pick disease patients

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