Update in the genetics of thalassemia: What clinicians need to know

Shang, Xuan; Xu, Xiang

doi:10.1016/j.bpobgyn.2016.10.012

Cited by 83 publications

(73 citation statements)

References 48 publications

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“…Our findings, and those from other studies (Hu et al , ; Clark et al , ), have proved that combinations of MLPA, array comparative genomic hybridization (array CGH) and NGS assays are very useful for identifying the known or unknown rearrangements in α‐ or β‐globin gene clusters. This duplication not only widens the spectrum of CNVs in globin genes but it is also the first report of a de novo large duplication, although some de novo point mutations have previously been found at this locus (Shang & Xu, ).…”

Section: Resultsmentioning

confidence: 80%

“…In the clinic, researchers and clinicians sometimes detect thalassaemia patients whose inheritance mode contradicts Mendelian laws. Many such patients can be explained by two mechanisms: (i) β‐thalassaemia carriers can co‐inherit a duplication of α‐globin ( HBA ) genes that results in thalassaemia intermedia (TI), or (ii) A de novo point mutation or large deletions combined with another mutation, inherited from the parents, which lead to thalassaemia (Hu et al , ; Shang & Xu, ). However, the origin of the de novo mutation is rarely analysed and there are still a small number of cases that are difficult to explain.…”

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confidence: 99%

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Thalassaemia intermedia caused by coinheritance of a β‐thalassaemia mutation and a de novo duplication of α‐globin genes in the paternal allele

et al. 2019

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Summary Next generation sequencing identified a de novo, 204 kb, tandem duplication (αααα204) in the α‐globin gene cluster of a Chinese thalassaemia intermedia patient. Haplotype analysis showed that the duplicated chromosome was of paternal origin. Molecular analysis of genomic DNA from the patient's lymphocytes, hair follicles, buccal mucosa cells, his father's lymphocytes and sperm cells excluded the possibility of somatic or germinal mosaicism. The analysis also indicated that this duplication arose during spermatogenesis. The microhomology in the breakpoint was found and suggested that this duplication could be formed by a coupled homologous and non‐homologous recombination mechanism.

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Section: Resultsmentioning

confidence: 80%

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confidence: 99%

Thalassaemia intermedia caused by coinheritance of a β‐thalassaemia mutation and a de novo duplication of α‐globin genes in the paternal allele

et al. 2019

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“…The 5′ breakpoint of these two deletions was very similar to this 223 kb deletion, both with a similar 5′ breakpoint to this case (Figure A). Three mechanisms may contribute to this different HbF level: (a) the 3′ breakpoints of the above two deletions were different from the present case; (b) the expression of HbF is regulated by many genetic modifiers such as XmnI polymorphism, KLF1, BCL11A, HBS1L, and MYB . The NGS data of our cases showed that they were all negative for mutations in these factors, while this information was absent for the carriers of the above two deletions; and (c) the 5′ breakpoint of the 223 kb deletion was not completely consistent in the above two deletions.…”

Section: Discussionmentioning

confidence: 99%

“…Most cases with β‐thalassemia are caused by point mutations or small deletions with several nucleotides lost in the beta‐globin gene . But deletions longer than 1 kb, which can be classified as large deletion, were also reported intermittently. Large deletions of the beta‐globin gene cluster reported previously have mostly been classified genetically into εγδβ 0 ‐thalassemia, ( G γ A γδβ) 0 ‐thalassemia, G γ( A γδβ) 0 ‐thalassemia, δβ 0 ‐thalassemia, and β 0 ‐thalassemia according to the gene(s) involved .…”

Section: Introductionmentioning

confidence: 99%

A novel 223 kb deletion in the beta‐globin gene cluster was identified in a Chinese thalassemia major patient

Zhu

Wei

Cai

et al. 2019

Int J Lab Hematology

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Introduction Although mutations in the human beta‐globin gene cluster are essentially point mutations, several large deletions have been described in recent years. Methods We have identified a novel 223 kb deletion in a Chinese patient by multiplex ligation‐dependent probe amplification and characterized it by next‐generation sequencing, Gap‐PCR, and DNA sequence analysis. Results The deletion extends from the 3′UTR of the δ globin gene (HBD) to 215 kb downstream of the HBB. Compound heterozygous with the typical β‐thalassemia—CD41‐42(‐CTTT) mutation, the proband presented with microcytosis and hypochromic red cells, and required regulate transfusion. The patient was clinically diagnosed with thalassemia major. Conclusion Our study widens the mutation spectrum of β‐thalassemia. In addition, this case may spark future studies of the regulatory regions of the beta‐globin gene cluster.

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“…Mutations in the alpha or beta globin genes can cause abnormal variants of HbA (hemoglobinopathies, such as sickle cell disease) or a decrease in production of one of the respective globin chain types (thalassemia) [17]. Alpha thalassemia is usually caused by a deletion of one or more of the alpha globin genes, leading to a decrease in alpha chain production and a relative excess of beta chains.…”

Section: Genetics Of Alpha and Beta Thalassemiamentioning

confidence: 99%

Distinguishing iron deficiency anaemia from thalassemia trait in clinical obstetric practice

Akers¹,

Howard²,

Ford³

2018

J Pregnancy Reprod

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Anaemia in pregnancy is common, occurring in approximately 38% of pregnancies. Iron deficiency anaemia (IDA) accounts for most cases (55% -70%) depending on the population being studied. However, both alpha and beta thalassemia trait cause microcytic, hypochromic anaemia and are commonly misdiagnosed as IDA. Thalassemia trait (or minor) should be considered when there is a microcytic anaemia that is not improving with iron therapy or when anaemia predates the pregnancy, especially in a patient from a high risk ethnic group. Also, certain features on the complete blood count (CBC) indices can suggest thalassemia trait such as microcytosis out of proportion to the anaemia along with a raised RBC count. A diagnosis of beta thalassemia trait can be made by the detection of an elevated Hb A2. A diagnosis of alpha thalassemia trait can be made by demonstrating Hemoglobin H bodies on the peripheral blood smear using special stains. In some thalassemia patients with equivocal phenotypic results, genetic testing for specific thalassemia mutations may be required. Identification of women with thalassemia trait is important for genetic counselling as well as avoiding unnecessary iron replacement therapy.

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Update in the genetics of thalassemia: What clinicians need to know

Cited by 83 publications

References 48 publications

Thalassaemia intermedia caused by coinheritance of a β‐thalassaemia mutation and a de novo duplication of α‐globin genes in the paternal allele

Thalassaemia intermedia caused by coinheritance of a β‐thalassaemia mutation and a de novo duplication of α‐globin genes in the paternal allele

A novel 223 kb deletion in the beta‐globin gene cluster was identified in a Chinese thalassemia major patient

Distinguishing iron deficiency anaemia from thalassemia trait in clinical obstetric practice

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