Characterization of three new deletions in the β-globin gene cluster during a screening survey in two French urban areas

Pissard, Serge; Raclin, Valérie; Lacan, Philippe; Garcia, Cyrielle; Aguilar-Martinez, Patricia; Francina, Alain; Joly, Philippe

doi:10.1016/j.cca.2012.08.030

Cited by 10 publications

(7 citation statements)

References 27 publications

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“…Aside the high HbF level she presents a classical b 0 thal allele carrier phenotype. There is a large number of deletions in the b-cluster that are associated with elevated HbF, nevertheless, these deletions usually involve the complete loss of gamma, delta and/or beta genes (Andersson et al, 2007;Thein and Wood, 2009;Pissard et al, 2013). The particular deletion reported in this study causes the loss of third exon and the possible loss of the HBB 3' regulatory region (DNase I hypersensitive site; LOC110006319; Gene ID: 110006319), which includes multiple GATA1 binding protein sequences (https://www.ncbi.nlm.nih.gov/gene/107133510).…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

Three Mexican Families with β thalassemia intermedia with different molecular basis

Ldcr

Fjp

et al. 2019

Genet. Mol. Biol.

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“…Use of multiple MLPA assays containing tiled probes will make the process cumbersome and expensive. Although QF‐MPCRs have been described earlier, this method has not been used extensively which may be due to the lack of reproducibility of the previously reported protocols . We found the design of primers, amplification reaction conditions using specific enzymes and careful determination of the number of cycles in the exponential phase at which the quantitation is performed are important parameters for successful and reproducible copy number analysis.…”

Section: Discussionmentioning

confidence: 99%

Identification of rare and novel deletions that cause (δβ)⁰‐thalassaemia and hereditary persistence of foetal haemoglobin in Indian population

Mayuranathan

Rayabaram

Das

et al. 2014

European J of Haematology

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“…Ces deux méthodes permettent de détecter les larges délétions du cluster ␤-globine mais le profil délétionnel obtenu, c'est-à-dire la liste des loci délétés par rapport à ceux testés (10 à 20 généralement), ne permet pas une identification formelle de la délétion mais juste une orientation dans le meilleur des cas. Le diagnostic de certitude se fait par une réaction de gap-PCR spécifique avec des amorces choisies pour encadrer au plus près la délétion que l'on cherche à mettre en évidence [57] ( figure 13). Pour des délétions rares et/ou très larges et/ou non décrites dans la littérature, le profil délétionnel obtenu peut ne donner aucune orientation particulière sur la nature de la délétion.…”

Section: Délétionsunclassified

Beta-thalassemias: molecular, epidemiological, diagnostical and clinical aspects

Joly

Pondarré

Badens

2014

Annales De Biologie Clinique

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Les bêta-thalassémies représentent une des maladies autosomiques récessives les plus fréquentes dans le monde. En France, on dénombre 5 à 10 nouveaux cas de formes majeures ou intermédiaires par an pour une prévalence globale d'environ 500 malades pour lesquels la généralisation des traitements chélateurs du fer a permis d'augmenter de façon très importante l'espérance de vie depuis une vingtaine d'années. Au niveau moléculaire, environ 90 % des allèles bêta-thalassémiques sont représentés par des mutations ponctuelles caractérisables facilement par séquençage Sanger ou par des techniques dédiées. Les 10 % restants sont des délétions plus ou moins larges détectables par MLPA ou par CGH Array. La détermination du génotype alpha est capitale dans l'exploration génétique d'une bêta-thalassémie puisqu'une alpha-thalassémie améliore la clinique tandis qu'une triplication alpha l'aggrave. Le génotypage additionnel d'autres polymorphismes inducteurs d'HbF permet même, au moyen d'un algorithme dédié, de prévoir l'âge de la première transfusion, faisant de la bêta-thalassémie l'une des premières applications potentielles de la médecine prédictive. Thérapie génique, diagnostic pré-implantatoire et nouveaux traitements médicamenteux (Sotatercept®, agonistes de l'hepcidine) achèvent de placer la ␤-thalassémie au-devant de l'actualité scientifique.Abstract. Beta-thalassemia is one of most common autosomal recessive disorders worldwide. In France, 5 to 10 new major or intermedia forms are diagnosed annually and the global prevalence is about 500 cases. Since 20 years and thanks to the generalization of iron chelator treatments, the life expectancy has dramatically increased. Nearly 90% of the ␤-thalassemic alleles are point mutations easily identified by Sanger sequencing or dedicated methods. The remaining 10% are deletions detectable by MLPA or CGH Array. The alphaglobin genotype is also essential in the exploration of beta-thalassemia because an alpha-thalassemia improves the clinical state whereas an alpha triplication worsens it. The additional genotyping of a few HbF inducer polymorphisms allows to predict the age of the first transfusion, thanks to a recent dedicated algorithm, making beta-thalassemia one of the first potential application of predictive medicine. Gene therapy, pre-implantatory diagnosis and new drugs (Sotatercept®, hepcidin-like molecules) have also recently contributed to make beta-thalassemia a main scientific topic again.

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Characterization of three new deletions in the β-globin gene cluster during a screening survey in two French urban areas

Cited by 10 publications

References 27 publications

Three Mexican Families with β thalassemia intermedia with different molecular basis

Three Mexican Families with β thalassemia intermedia with different molecular basis

Identification of rare and novel deletions that cause (δβ)⁰‐thalassaemia and hereditary persistence of foetal haemoglobin in Indian population

Beta-thalassemias: molecular, epidemiological, diagnostical and clinical aspects

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Characterization of three new deletions in the β-globin gene cluster during a screening survey in two French urban areas

Cited by 10 publications

References 27 publications

Three Mexican Families with β thalassemia intermedia with different molecular basis

Three Mexican Families with β thalassemia intermedia with different molecular basis

Identification of rare and novel deletions that cause (δβ)0‐thalassaemia and hereditary persistence of foetal haemoglobin in Indian population

Beta-thalassemias: molecular, epidemiological, diagnostical and clinical aspects

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Identification of rare and novel deletions that cause (δβ)⁰‐thalassaemia and hereditary persistence of foetal haemoglobin in Indian population