A new α0-thalassemia deletion found in a Dutch family (--AW)

Phylipsen, Marion; Vogelaar, Ingrid P.; Schaap, Rianne; Arkesteijn, Sandra G.J.; Boxma, George L.; Helden, W. C. H. van; Wildschut, Irene C.M.; Bruin-Roest, Andrea C. de; Giordano, Piero C.; Harteveld, Cornelis L.

doi:10.1016/j.bcmd.2010.05.004

Cited by 15 publications

(11 citation statements)

References 11 publications

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“…In addition, we compared the deletion pattern found in this family with those reported for common HBA deletion types and we found that the deletion that most closely resembles this novel one is the Dutch I α-zero type. 11 However, following the use of additional probes which extended the region analyzed, the MLPA pattern for this deletion did not exactly corresponded to the Dutch I type. With respect to the Dutch I, −KOZANI is a larger deletion because it involves two other probes: the 364 nt probe (probe name: Concluding, this presentation shows the benefit of combining hematological analysis with advanced molecular techniques, like MLPA, to detect novel thalassemia deletions in rare cases with unexplained microcytic anemia.…”

Section: Case Presentation With Resultsmentioning

confidence: 95%

“…The latter condition is incompatible with extrauterine life 7. In addition, we compared the deletion pattern found in this family with those reported for common HBA deletion types and we found that the deletion that most closely resembles this novel one is the Dutch I α-zero type 11. However, novel or rare deletions remain undetected using this conventional molecular technique.…”

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confidence: 79%

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Diagnosis and molecular characterization of a novel α⁰‐thalassemia deletion (–Kozani) found in a Greek child with unexplained microcytic hypochromic anemia

Makis

Georgiou

Traeger-Synodinos

et al. 2017

Int J Lab Hematology

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Section: Case Presentation With Resultsmentioning

confidence: 95%

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confidence: 79%

Diagnosis and molecular characterization of a novel α⁰‐thalassemia deletion (–Kozani) found in a Greek child with unexplained microcytic hypochromic anemia

Makis

Georgiou

Traeger-Synodinos

et al. 2017

Int J Lab Hematology

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“…Besides these most common deletions, a large variety of fewer occurring thalassemia deletions have been found in Chinese (8)(9)(10)(11)(12) and other populations (13)(14)(15)(16)(17)(18)(19)(20)(21). This report characterizes a novel a-thal deletion in a family from Shenzhen in Southern China, which removed 28.5 kb from the a-globin gene cluster, including the a1 and a2 genes; only the a1 gene was still present.…”

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confidence: 86%

AnAluElement-Mediated 28.5 kb α-Thalassemia Deletion Found in a Chinese Family

Xie

Luo

et al. 2014

Hemoglobin

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Over 95.0% of the α-thalassemia (α-thal) cases in southern China are caused by large deletions involving the α-globin gene. Here, we describe the molecular characterization of a novel 28.5 kb deletion that eliminated one of the duplicated α-globin genes in a Chinese family. The deletion breakpoint fragment involved Alu repeat sequences, suggesting a homologous recombination event. Phenotypic analysis on the heterozygous carrier of this deletion revealed that it leads to a very mild phenotype. Because of a 25.0% risk of Hb H (β4) disease in the offspring when in combination with another α(0)-thal allele, we should not ignore screening the deletion in prenatal diagnosis in order to decrease reproductive risk.

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“…Since then, multiple investigators have used MLPA to assess for a variety of deletions and mutations within the ␣-globin gene cluster and flanking genes. [11][12][13][14][15] A majority of these publications use MLPA primarily as a tool for detecting and classifying novel deletions that remain uncharacterized by prior testing methods such as SB, sequence analysis, and gap- ) was correct (SB result was misinterpreted).…”

Section: Discussionmentioning

confidence: 99%

Development and Clinical Implementation of a Combination Deletion PCR and Multiplex Ligation-Dependent Probe Amplification Assay for Detecting Deletions Involving the Human α-Globin Gene Cluster

Kipp

Roellinger

Lundquist

et al. 2011

The Journal of Molecular Diagnostics

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The ␣-thalassemias are a group of hereditary disorders caused by reduced synthesis of the ␣-chain of hemoglobin. We have developed and tested an ␣-thalassemia assay that uses both multiplex ligationdependent probe amplification (MLPA) with Luminex-based detection and deletion PCR technologies. The MLPA assay consisted of 20 probes, 15 of which hybridized to the ␣-globin gene cluster and 5 that served as control probes. A PCR assay was developed to confirm the presence of heterozygous/homozygous 3.7-kb and 4.2-kb deletions. MLPA and PCR results were compared to Southern blot (SB) results from 758 and 133 specimens, respectively. Lastly, MLPA and PCR results were reviewed and summarized from 5386 clinically tested specimens. SB and MLPA results were concordant in 678/687 (99%) specimens. PCR detected all deletions detected by SB with no false positives. No deletions or duplications were identified in 2630 (49%) clinically tested specimens. Extra ␣-globin copies were identified in 76 patients. A deletion of one or two ␣-globin genes was identified in 1251 (23%) and 1349 (25%) specimens, respectively, including 15 different genotypes. A deletion of three (hemoglobin H) and four ␣-globin genes (Hb Bart's) was observed in 65 or 3 specimens, respectively. Six patients had a deletion within the ␣-globin regulatory region MCS-R2. Thus, MLPA plus deletion PCR identify multiple ␣-globin gene deletions/duplications in patients being tested for ␣-thalassemia. The ␣-thalassemias are a group of recessively inherited disorders caused by reduced or absent synthesis of the ␣-chain of hemoglobin (Hb). Approximately 5% of the world's population is thought to be affected by ␣-thalassemia, making it one of the most common genetic disorders.1 Because of its selective advantage, the carrier rate of ␣-thalassemia is extremely high (Ͼ90%) in tropical and subtropical regions with a history of endemic malaria. 2The phenotype of patients with ␣-thalassemia is variable depending on the number of dysfunctional or absent ␣-globin genes. Patients with one dysfunctional ␣-globin gene (silent carrier) are often asymptomatic and unaware they have the genetic disorder unless they have a complete blood count examined. Similarly, patients with a deletion of two of the four ␣-globin genes (␣-thalassemia trait) may be asymptomatic and require no specific treatment. Hemoglobin H (three ␣-globin genes deleted/dysfunctional) is often more serious and is characterized by microcytic hypochromic hemolytic anemia, splenomegaly, and jaundice. All four of the ␣-globin alleles are dysfunctional in patients with Hb Bart's, the most severe and often fatal form of ␣-thalassemia. 2,3The two genes responsible for synthesis of the ␣-chain of Hb, HBA1 and HBA2, are located in the telomeric region on chromosome 16 (16p13.3) and encode ␣ 1 -globin and ␣ 2 -globin, respectively.2 These two genes are embedded within two highly homologous 4-kb duplication units that can be subdivided into separate homology blocks, written X, Y, and Z.2 Misalignment and recombination within ...

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A new α0-thalassemia deletion found in a Dutch family (--AW)

Cited by 15 publications

References 11 publications

Diagnosis and molecular characterization of a novel α⁰‐thalassemia deletion (–Kozani) found in a Greek child with unexplained microcytic hypochromic anemia

Diagnosis and molecular characterization of a novel α⁰‐thalassemia deletion (–Kozani) found in a Greek child with unexplained microcytic hypochromic anemia

AnAluElement-Mediated 28.5 kb α-Thalassemia Deletion Found in a Chinese Family

Development and Clinical Implementation of a Combination Deletion PCR and Multiplex Ligation-Dependent Probe Amplification Assay for Detecting Deletions Involving the Human α-Globin Gene Cluster

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A new α0-thalassemia deletion found in a Dutch family (--AW)

Cited by 15 publications

References 11 publications

Diagnosis and molecular characterization of a novel α0‐thalassemia deletion (–Kozani) found in a Greek child with unexplained microcytic hypochromic anemia

Diagnosis and molecular characterization of a novel α0‐thalassemia deletion (–Kozani) found in a Greek child with unexplained microcytic hypochromic anemia

AnAluElement-Mediated 28.5 kb α-Thalassemia Deletion Found in a Chinese Family

Development and Clinical Implementation of a Combination Deletion PCR and Multiplex Ligation-Dependent Probe Amplification Assay for Detecting Deletions Involving the Human α-Globin Gene Cluster

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Product

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Diagnosis and molecular characterization of a novel α⁰‐thalassemia deletion (–Kozani) found in a Greek child with unexplained microcytic hypochromic anemia

Diagnosis and molecular characterization of a novel α⁰‐thalassemia deletion (–Kozani) found in a Greek child with unexplained microcytic hypochromic anemia