Contrasting co-inheritance of alpha and beta mutations in delta beta thalassemia and hereditary persistence of fetal hemoglobin: a study from India

Pandey, Hareram; Ranjan, Ratnesh; Singh, Kanwaljeet; Sharma, Amit Kumar; Kishor, Kamal; Seth, Tulika; Saxena, Renu

doi:10.1080/10245332.2018.1458934

Cited by 12 publications

(8 citation statements)

References 20 publications

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“…In the areas where thalassemia is prevalent, detecting deletional HPFH/δβ‐thalassemia and δ‐globin gene mutation is important, as coexistence of HPFH or δ‐thalassemia with α‐ or β‐thalassemia will lead to the misdiagnosis and missed diagnosis of thalassemia (Chen, Huang, Zhou, & Li, ). Deletional HPFH/δβ‐thalassemia and δ‐thalassemia mutations are variable within different human populations (Pandey et al, ). Characterizing the spectrum and frequency of deletional HPFH/δβ‐thalassemia and δ‐thalassemia is vital for prenatal diagnosis programs for thalassemia.…”

Section: Discussionmentioning

confidence: 99%

“…Deletional HPFH and δβ‐thalassemia (deletional HPFH/δβ‐thalassemia) is a rare inherited condition that is characterized by increased Hb F, which results from deletions in the upstream silencer region of the γ‐globin genes or upregulation of the γ‐globin genes (Sankaran, Xu, & Orkin, ), as there is no competition from the expression of β‐ and δ‐globin genes. Deletional HPFH/δβ‐thalassemia may lead to the clinical phenotypes of heterogeneous β‐thalassemia with microcytic hypochromic red cell parameters (Pandey et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Analysis of deletional hereditary persistence of fetal hemoglobin/δβ‐thalassemia and δ‐globin gene mutations in Southerwestern China

Zhang

Yang

et al. 2019

Molec Gen & Gen Med

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Background Deletional hereditary persistence of fetal hemoglobin (HPFH)/δβ‐thalassemia and δ‐thalassemia are rare inherited disorders which may complicate the diagnosis of β‐thalassemia. The aim of this study was to reveal the frequency of these two disorders in Southwestern China. Methods A total of 33,596 subjects were enrolled for deletional HPFH/δβ‐thalassemia, and positive individuals with high fetal hemoglobin (Hb F) level were diagnosed by multiplex ligation‐dependent probe amplification (MLPA). A total of 17,834 subjects were analyzed for mutations in the δ‐globin gene. Positive samples with low Hb A2 levels were confirmed by δ‐globin gene sequencing. Furthermore, the pathogenicity and construction of a selected δ‐globin mutation were analyzed. Results A total of 92 suspected cases with Hb F ≥5.0% were further characterized by MLPA. Eight different deletional HPFH/δβ‐thalassemia were observed at a frequency of 0.024%. In addition, 195 cases suspected to have a δ‐globin gene mutation (Hb A2 ≤2.0%) were characterized by molecular analysis. δ‐Globin gene mutation was found at a frequency of 0.49% in Yunnan. The pathogenicity and construction for a selected δ‐globin mutation was predicted. Conclusion Screening of these two disorders was analyzed in Southwestern China, which could define the molecular basis of these conditions in this population.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Analysis of deletional hereditary persistence of fetal hemoglobin/δβ‐thalassemia and δ‐globin gene mutations in Southerwestern China

Zhang

Yang

et al. 2019

Molec Gen & Gen Med

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“…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%

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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“…Deletional HPFH/δβ-thalassemia typically results in a clinical phenotype with microcytic hypochromic anemia. Moreover, coinheritance with minor β-thalassemia or Hb variants in the β-globin chain has been identified to cause thalassemia intermedia or major, although clinical phenotypes vary [4][5][6][7][8]. In general, the identification of carriers plays an important role in prenatal diagnosis, especially in regions with high β-thalassemia occurrence.…”

Section: Introductionmentioning

confidence: 99%

Molecular epidemiology and hematologic characterization of δβ-thalassemia and hereditary persistence of fetal hemoglobin in 125,661 families of greater Guangzhou area, the metropolis of southern China

Jiang

Zuo

et al. 2020

BMC Med Genet

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Background: Individuals with δβ-thalassemia/HPFH and β-thalassemia usually present with intermedia or thalassemia major. No large-scale survey on HPFH/δβ-thalassemia in southern China has been reported to date. The purpose of this study was to examine the molecular epidemiology and hematologic characteristics of these disorders in Guangzhou, the largest city in Southern China, to offer advice for thalassemia screening programs and genetic counseling. Methods: A total of 125,661 couples participated in pregestational thalassemia screening. 654 subjects with fetal hemoglobin (HbF) level ≥ 5% were selected for further investigation. Gap-PCR combined with Multiplex ligation dependent probe amplification (MLPA) was used to screen for β-globin gene cluster deletions. Gene sequencing for the promoter region of HBG1 /HBG2 gene was performed for all those subjects. Results: A total of 654 individuals had hemoglobin (HbF) levels≥5, and 0.12% of the couples were found to be heterozygous for HPFH/δβ-thalassemia, including Chinese G γ ( A γδβ) 0 -thal, Southeast Asia HPFH (SEA-HPFH), Taiwanese deletion and Hb Lepore-Boston-Washington. The highest prevalence was observed in the Huadu district and the lowest in the Nansha district. Three cases were identified as carrying β-globin gene cluster deletions, which had not been previously reported. Two at-risk couples (0.0015%) were required to receive prenatal diagnosis. We also found 55cases of nondeletional-HPFH (nd-HPFH), including 54 with Italian nd-HPFH and one with the A γ-197C-T heterozygous state. It is difficult to discriminate between Chinese G γ ( A γδβ) 0 -thal and Italian nd-HPFH carriers using hemoglobin (Hb) analysis. (Continued on next page)Conclusions: This study is the first to describe the familial prevalence of HPFH/δβ-thalassemia and the high-risk rate in Greater Guangzhou Area, and the findings will support the implementation of thalassemia screening for three common deletions by gap-PCR. We also presented a systematic description of genotype-phenotype relationships which will be useful for genetic counseling and prenatal diagnostic services for β-thalassemia intermedia.

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Contrasting co-inheritance of alpha and beta mutations in delta beta thalassemia and hereditary persistence of fetal hemoglobin: a study from India

Cited by 12 publications

References 20 publications

Analysis of deletional hereditary persistence of fetal hemoglobin/δβ‐thalassemia and δ‐globin gene mutations in Southerwestern China

Analysis of deletional hereditary persistence of fetal hemoglobin/δβ‐thalassemia and δ‐globin gene mutations in Southerwestern China

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

Molecular epidemiology and hematologic characterization of δβ-thalassemia and hereditary persistence of fetal hemoglobin in 125,661 families of greater Guangzhou area, the metropolis of southern China

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