Detection of germline rearrangements in patients with α- and β-thalassemia using high resolution array CGH

Blattner, Ariane C.; Brunner-Agten, Saskia; Ludin, Katja; Hergersberg, Martin; Herklotz, Roberto; Huber, Andreas; Röthlisberger, Benno

doi:10.1016/j.bcmd.2013.02.002

Cited by 15 publications

(7 citation statements)

References 34 publications

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“…MLPA or array CGH, or the combination of MLPA and CGH, is a reliable method to screen for α and β gene rearrangements in thalassemia and hemoglobinopathy [18][19][20]. In this study, we first screened for the α gene copy number alterations using MLPA.…”

Section: Discussionmentioning

confidence: 99%

Thalassemia Intermedia Caused by 16p13.3 Sectional Duplication in a β-Thalassemia Heterozygous Child

Jiang

et al. 2015

Pediatric Hematology and Oncology

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Thalassemia intermedia is an inherited hemoglobin disorder characterized by a significant genetic and clinical heterogeneity. A wide spectrum of different genotypes-homozygous, heterozygous, and compound heterozygous-have been found to be responsible for it. The authors describe a Chinese child of β-thalassemia heterozygote with the mutation IVS2-654 (C→T) (HBB:c.316-197C→T) presenting with severe thalassemia intermedia. Multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (CGH) analyses of the α gene cluster revealed an approximate 146-kb duplication at 16p13.3 including the complete α gene cluster. The duplicated allele and the normal allele in trans result in a total of 6 active α genes. The severe clinical phenotype seemed to be related to the considerable excess of the α-globin and the β-globin deficit caused by the presence of the β-thalassemia. The α gene duplication should be considered in patients heterozygous for β-thalassemia who show a more severe phenotype than β-thalassemia trait.

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Section: Discussionmentioning

confidence: 99%

Thalassemia Intermedia Caused by 16p13.3 Sectional Duplication in a β-Thalassemia Heterozygous Child

Jiang

et al. 2015

Pediatric Hematology and Oncology

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“…It was also possible to identify the −α 3.7 and −α 4.2 single‐gene deletions, although the results were difficult to interpret a priori due to the similarity of HBA1 and HBA2 sequences, resulting in cross‐hybridization 22 . Similar approaches have been used by others 23–25 …”

Section: Molecular Diagnosis Of Globin Disordersmentioning

confidence: 98%

“…22 Similar approaches have been used by others. [23][24][25] For non-deletional α-thalassemia, Sanger DNA sequencing can be used to detect all point mutations. Allele-specific PCR also has a role in areas where certain mutations are common, such as hemoglobin Constant Spring in Southeast Asia.…”

Section: α-Thalassemiamentioning

confidence: 99%

“…20,43 We and others have demonstrated the ability of array-CGH to characterize deletions of the HBB locus. [22][23][24][25] Due to close spacing of probes, array-CGH can finely map deletion breakpoints, allowing the design of PCR primers to amplify the breakpoint region and to determine the breakpoint sequences. We used this technique to demonstrate the breakpoints responsible for several types of δβ-thalassemia and HPFH.…”

Section: β-Thalassemiamentioning

confidence: 99%

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The role of molecular diagnostic testing for hemoglobinopathies and thalassemias

Sabath

2023

Int J Lab Hematology

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Hemoglobin disorders are among the most common genetic diseases worldwide. Molecular diagnosis is helpful in cases where the diagnosis is uncertain and for genetic counseling. Protein‐based diagnostic techniques are frequently adequate for initial diagnosis. Molecular genetic testing is pursued in some cases, particularly when a definitive diagnosis is not possible and especially for the purpose of assessing genetic risk for couples wanting to have children. The expertise available in the clinical hematology laboratory is essential for the diagnosis of patients with hemoglobin abnormalities. Initial diagnoses are made using protein‐based techniques such as electrophoresis and chromatography. Based on these findings, genetic risk to an individual's offspring can be assessed. In the setting of β‐thalassemia and other β‐globin disorders, coincident α‐thalassemia may be difficult to diagnose, which can have potentially serious consequences. In addition, unusual forms of β‐thalassemia caused by deletions in the β‐globin locus cannot be definitively characterized using standard techniques. Molecular diagnostic testing has an important role in the diagnosis of hemoglobin disorders and is important in the setting of genetic counseling. Molecular testing also has a role in prenatal diagnosis to identify fetuses affected by severe hemoglobinopathies and thalassemias.

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“…These arrays use probes spaced at short intervals throughout the locus to finely map the deletion breakpoints, to design PCR primers to amplify the breakpoint region and to determine the sequences flanking the breakpoints. This technique is employed to confirm the breakpoints for several known mutations causing δβ-thalassemia and hereditary persistence of fetal hemoglobin (HPFH) as well as previously unmapped deletions [ 17 , 18 , 19 , 20 ]. In such cases, multiplex ligation-dependent amplification (MLPA) may be used to determine the presence of an unidentified α- or β-globin gene deletion, by assessing DNA copy number changes.…”

Section: Carrier Screeningmentioning

confidence: 99%

From Prenatal to Preimplantation Genetic Diagnosis of β-Thalassemia. Prevention Model in 8748 Cases: 40 Years of Single Center Experience

Monni

Peddes

Iuculano

et al. 2018

JCM

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The incidence of β-thalassemia in Sardinia is high and β-39 is the most common mutation. The prevention campaign started in 1977 and was performed in a single center (Microcitemico Hospital, Cagliari, Sardinia, Italy). It was based on educational programs, population screening by hematological and molecular identification of the carriers. Prenatal and pre-implantation diagnosis was offered to couples at risk. 8564 fetal diagnosis procedures using different invasive approaches and analysis techniques were performed in the last 40 years. Trans-abdominal chorionic villous sampling was preferred due to lower complication risks and early diagnosis. Chorionic villous DNA was analyzed by PCR technique. 2138 fetuses affected by β-thalassemia were diagnosed. Women opted for termination of the pregnancy (TOP) in 98.2% of these cases. Pre-implantation genetic diagnosis (PGD) was proposed to couples at risk to avoid TOP. A total of 184 PGD were performed. Initially, the procedure was exclusively offered to infertile couples, according to the law in force. The success rate of pregnancies increased from 11.1% to 30.8% when, crucial law changes were enacted, and PGD was offered to fertile women as well. Forty years of β-thalassemia prevention programs in Sardinia have demonstrated the important decrease of this severe genetic disorder.

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Detection of germline rearrangements in patients with α- and β-thalassemia using high resolution array CGH

Cited by 15 publications

References 34 publications

Thalassemia Intermedia Caused by 16p13.3 Sectional Duplication in a β-Thalassemia Heterozygous Child

Thalassemia Intermedia Caused by 16p13.3 Sectional Duplication in a β-Thalassemia Heterozygous Child

The role of molecular diagnostic testing for hemoglobinopathies and thalassemias

From Prenatal to Preimplantation Genetic Diagnosis of β-Thalassemia. Prevention Model in 8748 Cases: 40 Years of Single Center Experience

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