Polymerase chain reaction amplification applied to the direct detection of a 4 bp deletion in the promoter region of the <sup>A</sup>γ gene

Manca, Laura; Cocco, Elena; Masala, Bruno Lucio; Gilman, J. G.

doi:10.1002/ajh.2830350215

Cited by 7 publications

(3 citation statements)

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“…In particular, amplification of the gene promoter region spanning positions -617 to +45 relative to the cap site was performed as previously reported [21]. The 4 bp deletion at -225 to -222 of the *yT promoter was directly detected by Fnu4HI digestion of PCR amplified target DNA as described [22]. The (C-T) mutation at position -158 of the Gy gene promoter [23] was studied by XmnI digestion of DNA selectively amplified by PCR (from -623 to…”

Section: Methodsmentioning

confidence: 99%

Fetal hemoglobin expression in compound heterozygotes for −117 (G→A) ^Aγ HPFH and β⁰39 nonsense thalassemia

Pistidda¹,

Frogheri²,

Oggiano³

et al. 1995

American J Hematol

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The -117(G-->A)A gamma hereditary persistence of fetal hemoglobin (Greek HPFH) and beta zero 39-thal mutations are rather frequent in Sardinia so that their interaction is to be expected. Characterization of eight compound heterozygotes for these defects indicated that HPFH was linked to haplotype VII and beta zero 39-thal to haplotype II. Haplotype II beta zero 39-thal chromosome carries the A gamma T gene which is a useful marker of gamma-gene expression. Since the Hb F level in these compound heterozygotes was significantly higher than in 46 -117 HPFH carriers, the A gamma I, A gamma T, and G gamma globin level was determined. A gamma T was underexpressed while G gamma was significantly increased, which suggest that in -117 A gamma HPFH/beta zero 39-thal healthy subjects the increase in Hb F production is determined only by the -117 mutated A gamma gene and the adjacent G gamma gene.

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Section: Methodsmentioning

confidence: 99%

Fetal hemoglobin expression in compound heterozygotes for −117 (G→A) ^Aγ HPFH and β⁰39 nonsense thalassemia

Pistidda¹,

Frogheri²,

Oggiano³

et al. 1995

American J Hematol

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“…Similar results were later obtained by others (81, 82). The presence of the −AGCA deletion is easily and directly detected by means of Fnu 4HI digestion of the A γ genes amplified by PCR (83). Another 4 bp deletion (−AAGC) occurring at position −226 to −223 of the promoter of the same A γ T gene has been observed in a Chinese family (84).…”

Section: The Hbf Variantsmentioning

confidence: 99%

Disorders of the synthesis of human fetal hemoglobin

Manca

Masala

2008

IUBMB Life

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Fetal hemoglobin (HbF), the predominant hemoglobin in the fetus, is a mixture of two molecular species (α2Gγ2 and α2Aγ2) that differ only at position 136 reflecting the products of two nonallelic γ‐globin genes. At the time of birth, HbF accounts for ∼70% of the total Hb. The Gγ:Aγ globin ratio in the HbF of normal newborn is 70:30 whereas in the trace amounts of HbF that is found in the adult it reverses to 40:60 because of a γ‐ to β‐globin gene switch. Alterations of these ratios are indicative of a molecular defect at the level of the HbF synthesis. Qualitative hemoglobinopathies due to Gγ and Aγ chain structural variants, and quantitative hemoglobinopathies affecting the synthesis of HbF such as γ‐thalassemias, duplications, triplications, and even sextuplications of the γ‐globin genes, which may be detected in newborn blood lysates, have been described. Moreover, several pathological and nonpathological conditions affecting the β‐globin gene cluster, such as β‐thalassemia, sickle cell disease, δβ‐thalassemia, and hereditary persistence of HbF syndromes, are characterized by the continued synthesis of γ‐globin chains in the adult life. Studies of these natural mutants associated with increased synthesis of HbF in adult life have provided considerable insight into the understanding of the control of globin gene expression and Hb switching. © 2008 IUBMB IUBMB Life, 60(2): 94–111, 2008

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“…DNA extraction and Sutton's Haplotype on the b-globin gene cluster were performed as reported for nine restriction fragment length polymorphisms (RFLPs) in the b-gene complex: Hinc II-e, Xmn I-G c, Hind III-G c, Hind III-A c, Hinc II-wb, Hinc II-3kwb, Hinf I-5kb, Ava II-b and RSA I-3kb (15). To determine the presence or absence of the 4bp deletion 5k to A c, A c promoter DNA (x622 to +53) was ampli®ed by the polymerase chain reaction (PCR) (16). The presence of the Greek HPFH mutation was determined by the denaturating gradient gel electrophoresis technique (DGGE) as previously described (17).…”

Section: Subjectsmentioning

confidence: 99%

Fetal hemoglobin expression in the compound heterozygous state for−117 (G→A) ^Aγ HPFH and IVS‐1 nt 110 (G→A) β⁺ thalassemia: a case study

Dedoussis

Sinopoulou

Gyparaki

et al. 2000

European J of Haematology

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The splicing defect at IVS-I-110 is by far (43.15%) the most common beta-thalassaemia mutation in Greece. The - 117 (G-->A) Agamma hereditary persistence of fetal hemoglobin (Greek HPFH) is also the most frequent nondeletional HPFH in Greece. We report a case in which these two defects co-segregates. She is a healthy female where the total Hb is 12.3 g/dl with 51% HbF and normal HbA2. Her Ggamma/Agamma ratio is 35:65 differing from that of 10 simple heterozygotes for the Greek HPFH who have ratio of 8:92. Molecular analysis of the beta-globin genotype revealed the presence of the IVS-I-110 beta+ mutation in trans to the -117 G-->A Greek HPFH. Both mutations are linked to Ia. Her father has Greek HPFH in trans to the -158 C-->T on the Ggamma promoter, which is linked with haplotype IIIalpha. He has 13% HbF with a Ggamma/Agamma ratio 32:68. Her sister is a compound heterozygote for the IVS-I-110 mutation in trans to the - 158 C-->T, with HbF levels of 3% and a Ggamma/Agamma ratio 72:28.

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Polymerase chain reaction amplification applied to the direct detection of a 4 bp deletion in the promoter region of the ^Aγ gene

Cited by 7 publications

References 10 publications

Fetal hemoglobin expression in compound heterozygotes for −117 (G→A) ^Aγ HPFH and β⁰39 nonsense thalassemia

Fetal hemoglobin expression in compound heterozygotes for −117 (G→A) ^Aγ HPFH and β⁰39 nonsense thalassemia

Disorders of the synthesis of human fetal hemoglobin

Fetal hemoglobin expression in the compound heterozygous state for−117 (G→A) ^Aγ HPFH and IVS‐1 nt 110 (G→A) β⁺ thalassemia: a case study

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Polymerase chain reaction amplification applied to the direct detection of a 4 bp deletion in the promoter region of the Aγ gene

Cited by 7 publications

References 10 publications

Fetal hemoglobin expression in compound heterozygotes for −117 (G→A) Aγ HPFH and β039 nonsense thalassemia

Fetal hemoglobin expression in compound heterozygotes for −117 (G→A) Aγ HPFH and β039 nonsense thalassemia

Disorders of the synthesis of human fetal hemoglobin

Fetal hemoglobin expression in the compound heterozygous state for−117 (G→A) Aγ HPFH and IVS‐1 nt 110 (G→A) β+ thalassemia: a case study

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Polymerase chain reaction amplification applied to the direct detection of a 4 bp deletion in the promoter region of the ^Aγ gene

Fetal hemoglobin expression in compound heterozygotes for −117 (G→A) ^Aγ HPFH and β⁰39 nonsense thalassemia

Fetal hemoglobin expression in compound heterozygotes for −117 (G→A) ^Aγ HPFH and β⁰39 nonsense thalassemia

Fetal hemoglobin expression in the compound heterozygous state for−117 (G→A) ^Aγ HPFH and IVS‐1 nt 110 (G→A) β⁺ thalassemia: a case study