Dataset Information

Prenatal diagnosis of a rare ?-thalassemia gene ?90 (C>T) (HBB: c.-140 C>T) mutation associated with deletional Hb H disease (--SEA /-?4.2 ).

ABSTRACT: BACKGROUND:Hemoglobin H (Hb H) disease can be caused by compound heterozygosity for two different mutations or from homozygotes for mutations, and conventional genetic methods may lead to misdiagnosis when Hb H disease is combined with a rare ?-thalassemia. METHODS:Hematology parameters and hemoglobin electrophoresis analysis, gap-polymerase chain reaction (gap-PCR) and reverse dot-blot hybridization (RDB-PCR) were employed to identify common ?-thalassemia and Hb H disease. Rare ?-thalassemia mutations were detected by DNA sequencing. RESULTS:Hematological analysis and hemoglobin electrophoresis revealed a mild anemia ?0 -thalassemia trait (Hb 90 g/L, MCV 71 fL, and MCH 22.7 pg) compound with ?+ -thalassemia trait (MCV 71 fL, MCH 22.7 pg, and HbA2 5.51%) for the pregnant woman. DNA sequencing for the ?-globin gene revealed rare a ?90 (C>T) (HBB: c.-140 C>T) mutation for the woman. DNA analysis identified that the fetus inherited the ?0 -thalassemia mutation [--SEA (Southeast Asian)] and a rare ?+ -thalassemia mutation ?90 (C>T) (HBB: c.-140 C>T) from the mother, and the ?+ -thalassemia mutation [-?4.2 (leftward)] from the father. CONCLUSION:We reported a rare ?90 (C>T) (HBB: c.-140 C>T) mutation combined with the --SEA /-?4.2 in a family. This finding enriched the mutation spectrum of thalassemia molecular characteristics in China and emphasized the significance in DNA sequencing in mutation screening for the families with thalassemia.

SUBMITTER: Qian H

PROVIDER: S-EPMC7667371 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Prenatal diagnosis of a rare β-thalassemia gene －90 (C>T) (HBB: c.-140 C>T) mutation associated with deletional Hb H disease (--<sup>SEA</sup> /-α<sup>4.2</sup> ).

Qian Hou H Huang Jianlin J Xu Ji J Zhao Weihua W Ye Xiufeng X Liu Wenlan W

Molecular genetics & genomic medicine 20200903 11

<h4>Background</h4>Hemoglobin H (Hb H) disease can be caused by compound heterozygosity for two different mutations or from homozygotes for mutations, and conventional genetic methods may lead to misdiagnosis when Hb H disease is combined with a rare β-thalassemia.<h4>Methods</h4>Hematology parameters and hemoglobin electrophoresis analysis, gap-polymerase chain reaction (gap-PCR) and reverse dot-blot hybridization (RDB-PCR) were employed to identify common α-thalassemia and Hb H disease. Rare β ...[more]

PMID: 32885601

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Project description:Alpha-thalassemia is highly prevalent in the plural society of Brazil and is a public health problem. There is limited knowledge on its accurate frequency and distribution in the Amazon region. Knowing the frequency of thalassemia and the prevalence of responsible mutations is, therefore, an important step in the understanding and control program. Hematological and molecular data, in addition to serum iron and serum ferritin, from 989 unrelated first-time blood donors from Amazonas Hemotherapy and Hematology Foundation (FHEMOAM) were collected. In this study, the subjects were screened for -? 3.7/4.2/20.5, -SEA, -FIL, and -MED deletions. Alpha-thalassemia screening was carried out between 2016 and 2017 among 714 (72.1%) male and 275 (27.9%) female donors. The aims of this analysis were to describe the distribution of various alpha-thalassemia alleles by gender, along with their genotypic interactions, and to illustrate the hematological changes associated with each phenotype. Amongst the patients, 5.35% (n?=?53) were diagnosed with deletion -? -3.7 and only one donor with ? -4.2 deletion. From the individuals with -? -3.7, 85.8% (n?=?46) were heterozygous and 14.20% (n?=?7) were homozygous. The frequency of the -? -3.7 deletion was higher in male (5.89%) than in female (4.0%). There is no significant difference in the distribution of -? -3.7 by gender (p = 0.217). The -? 20.5, -SEA, and -MED deletions were not found. All subjects were analyzed for serum iron and serum ferritin, with 1.04% being iron deficient (n?=?5) and none with very high levels of stored iron (>220?µg/dL). Alpha-thalassemia-23.7kb deletion was the most common allele detected in Manaus blood donors, which is a consistent result, once it is the most common type of ?-thalassemia found throughout the world. As expected, the mean of hematological data was significantly lower in alpha-thalassemia carriers (p < 0.001), mainly homozygous genotype. Leukocytes and platelet count did not differ significantly. Due to the small number of individuals with iron deficiency found among blood donors, the differential diagnosis between the two types of anemia was not possible, even because minor changes were found among hematological parameters with iron deficiency and ?-thalassemia. Despite this, the study showed the values of hematological parameters, especially MCV and MCH, are lower in donors with iron deficiency, especially when associated with ?-thalassemia, and therefore, it may be useful to discriminate different types of microcytic anaemia. In conclusion, we believed screening for thalassemia trait should be included as part of a standard blood testing before blood donation. It should be noted that this was the first study to perform the screening for alpha deletions in blood donors from the Manaus region, and further studies are required to look at the effects of donated thalassemic blood.

Project description:BackgroundLow HbF expression in HbE-β+-thalassemia may lead to misdiagnosis of HbE heterozygosity. We aimed to characterize the β- and α-globin genes and the modifying factors related to HbF expression in patients with an Hb phenotype similar to that of HbE heterozygotes. Furthermore, screening tools for differentiating HbE-β+-thalassemia from HbE heterozygotes have been investigated.Participants and methodsA total of 2133 participants with HbE and HbA with varying HbF levels were recruited. Polymerase chain reaction-based DNA analysis and sequencing were performed to characterize β- and α-globin genes. DNA polymorphism at position -158 nt 5' to Gγ-globin was performed by XmnI restriction digestion. Receiver operating characteristic (ROC) curves were constructed using the area under the curve (AUC). Cutoff values of HbA2, HbE, and HbF levels for the differentiation of HbE-β+-thalassemia from HbE heterozygotes were determined.ResultsFive β+-thalassemia mutations trans to βE-gene (β-87(C>A), β-31(A>G), β-28(A>G), β19(A>G), and β126(T>G)) were identified in 79 patients. Among these, 54 presented with low HbF levels, and 25 presented with high HbF levels. ROC curve analysis revealed an excellent AUC of 1.000 (95% confidence interval:1.000-1.000) for HbE levels, and a cut-off point of ≥35.0% had 100.0% sensitivity, specificity, and Youden's index for differentiating HbE-β+-thalassemia from HbE heterozygotes. The proportion of α-thalassemia mutations was 46.3 and 8.0% among HbE-β+-thalassemia patients with low and high HbF levels, respectively. Two rare α-thalassemia mutations (Cap +14(C>G) and initiation codon (ATG>-TG)) of α2-globin genes were identified. The genotype and allele of the polymorphism at -158 nt 5' to Gγ-globin was found to be negatively associated with HbF expression.ConclusionsHbE-β+-thalassemia cannot be disregarded until appropriate DNA analysis is performed, and the detection of α-thalassemia mutations should always be performed under these conditions. An HbE level ≥35.0% may indicate screening of samples for DNA analysis for HbE-β+-thalassemia diagnosis.

Dataset Information

Prenatal diagnosis of a rare ?-thalassemia gene ?90 (C>T) (HBB: c.-140 C>T) mutation associated with deletional Hb H disease (--SEA /-?4.2 ).

Publications

Prenatal diagnosis of a rare β-thalassemia gene －90 (C>T) (HBB: c.-140 C>T) mutation associated with deletional Hb H disease (--<sup>SEA</sup> /-α<sup>4.2</sup> ).

Similar Datasets

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