Effects of α-thalassaemia mutations on the haematological parameters of β-thalassaemia carriers

Saleh‐Gohari, Nasrollah; Bami, Maryam Khademi; Nikbakht, Roshan; Karimi-Maleh, Hassan

doi:10.1136/jclinpath-2014-202825

Cited by 20 publications

(11 citation statements)

References 12 publications

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“…Their hematological data were consistent with previous reports of families carrying one b 0 -thal allele along with an a-cluster duplication (Harteveld et al, 2008;4 de la Torre et al Ben-Salah et al, 2017;Clark et al, 2018;Theodoridou et al, 2018). It is known that co-inheritance of a deletions represents a benefit for b-thal patients; on the other hand, increased a-globin chains due to genes duplication in bthal patients leads to a more severe phenotype (Mettananda et al, 2015;Saleh-Gohari et al, 2015;Shang and Xu 2017). Several studies demonstrate the common association of a-globin gene duplications and a single b-thal allele as a cause of b-thal intermedia (Origa et al, 2014).…”

Section: Discussionsupporting

confidence: 90%

Three Mexican Families with β thalassemia intermedia with different molecular basis

Ldcr

Fjp

et al. 2019

Genet. Mol. Biol.

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Beta thalassemia (b-thal) is a frequent monogenic disease, is clinically and molecularly heterogeneous. This study described molecular and laboratory findings for three Mexican patients with b-thal intermedia phenotype and their relatives. Three Mexican families were studied for presenting b-thal intermedia, ARMS-PCR and Gap-PCR were performed to screen for common mutations, Sanger sequencing for rare or new alleles, and MLPA for identifying deletions and or duplications. In all three families we observed, in heterozygote condition, the mutation c.118C > T (p.Gln39*) also known as codon 39(C > T) in the b globin gene (HBB) associated with a novel molecular defect: a new duplication of the alpha globin gene cluster, a new deletion that includes the loss of exon 3 of HBB and finally a novel mutation in the 3'UTR of HBB (HBB: c.*132C > A). We report three Mexican families with beta thalassemia intermedia due to different molecular basis; a new single nucleotide mutation involving the last nucleotide of the b-globin chain transcript; and two possible new DNA rearrangements, an a cluster duplication, and a partial b gene deletion.

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Section: Discussionsupporting

confidence: 90%

Three Mexican Families with β thalassemia intermedia with different molecular basis

Ldcr

Fjp

et al. 2019

Genet. Mol. Biol.

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“…The detection of HbE is essential for the diagnosis. In simple HbE trait, the HbE levels are 25-30% of the total Hb; the values of HbE vary when co-inherited with a-or b-traits [23,24] ( Table 1).…”

Section: Hbe Carriermentioning

confidence: 99%

Laboratory diagnosis of thalassemia

Brancaleoni

Pierro

Motta

et al. 2016

Int J Lab Hematology

159

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Summary The thalassemias can be defined as α‐ or β‐thalassemias depending on the defective globin chain and on the underlying molecular defects. The recognition of carriers is possible by hematological tests. Both α‐ and β‐thalassemia carriers (heterozygotes) present with microcytic hypochromic parameters with or without mild anemia. Red cell indices and morphology followed by separation and measurement of Hb fractions are the basis for identification of carriers. In addition, iron status should be ascertained by ferritin or zinc protoporphyrin measurements and the iron/total iron‐binding capacity/saturation index. Mean corpuscular volume and mean corpuscular hemoglobin are markedly reduced (mean corpuscular volume: 60–70 fl; MCH: 19–23 pg) in β‐thalassemia carriers, whereas a slight to relevant reduction is usually observed in α‐carriers. HbA2 determination is the most decisive test for β‐carrier detection although it can be disturbed by the presence of δ‐thalassemia defects. In α‐thalassemia, HbA2 can be lower than normal and it assumes significant value when iron deficiency is excluded. Several algorithms have been introduced to discriminate from thalassemia carriers and subjects with iron‐deficient anemia; because the only discriminating parameter is the red cell counts, these formulas must be used consciously. Molecular analysis is not required to confirm the diagnosis of β‐carrier, but it is necessary to confirm the α‐thalassemia carrier status. The molecular diagnosis is essential to predict severe transfusion‐dependent and intermediate‐to‐mild non‐transfusion‐dependent cases. DNA analysis on chorionic villi is the approach for prenatal diagnosis and the methods are the same used for mutations detection, according to the laboratory facilities and expertise.

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“…The second case was alpha‐thalassemia 1 trait with homozygous Hb E, with MCV 78.7 fL. There was evidence that double heterozygote state might influence the MCV value and result in misdiagnosis …”

Section: Discussionmentioning

confidence: 99%

Optimal cutoff of mean corpuscular volume (MCV) for screening of alpha‐thalassemia 1 trait

Nunchai

Sirichotiyakul

Tongsong

2020

J of Obstet and Gynaecol

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Aim: To identify the optimal cutoff of mean corpuscular volume (MCV) for screening of alpha-thalassemia 1 trait. Methods: The database of pregnant women who attended antenatal care clinic at Department of Obstetrics and Gynecology, Chiang Mai University during January 1st, 2015 to December 31st, 2017 was accessed and reviewed. A total of 1264 cases who had MCV ≤80 fL and met the inclusion criteria were enrolled to the study. Cases with hemoglobin level ≤10.0 gm/dL, iron deficiency anemia, chronic medical diseases and other types of thalassemia trait except alpha-thalassemia 1 trait were excluded. Results: After exclusion, 438 cases were available for analysis. Of them, 139 were alpha-thalassemia 1 trait. Based on the receiver operating characteristic curves, the best cutoff value of MCV for screening of alphathalassemia 1 trait was ≤76.15 fL, giving 100% sensitivity, and 60.9% specificity with the area under curve of 0.925. Compared to the conventional cutoff (≤80 fL), the new cutoff gave much less false positive tests (117 vs 299 cases), whereas capability to detect alpha-thalassemia 1 trait was the same. Conclusion: With the new MCV cutoff (≤76.15 fL) as a secondary cutoff for screening alpha-thalassemia 1 carrier, a substantial number of positive cases requiring DNA analysis could be avoided without compromising the detection efficacy.

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Effects of α-thalassaemia mutations on the haematological parameters of β-thalassaemia carriers

Cited by 20 publications

References 12 publications

Three Mexican Families with β thalassemia intermedia with different molecular basis

Three Mexican Families with β thalassemia intermedia with different molecular basis

Laboratory diagnosis of thalassemia

Optimal cutoff of mean corpuscular volume (MCV) for screening of alpha‐thalassemia 1 trait

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