Hemoglobin Chesterfield (beta 28 Leu----Arg) produces the phenotype of inclusion body beta thalassemia [letter]

Thein, SL; Best, Steven; Sharpe, John; Paul, Bindu D.; Clark, DJ; Brown, M. J.

doi:10.1182/blood.v77.12.2791.2791

Cited by 32 publications

(6 citation statements)

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“…Many of the heterozygous -globin missense variants that lead to unstable Hb variants occur in exon 3 [1], as most of the critical points leading to the interaction of the 11 dimer required for proper Hb assembly are encoded in this region [16,17]. However, a number of variants occurring in exon 1 and 2 that lead to critical interruptions in the Hb structure have also been described [1,4,7,8].…”

Section: Discussionmentioning

confidence: 99%

“…This typically results in a conformal change in the globin chain such that the tetramer cannot form properly, or the assembled hemoglobin (Hb) is unstable and is rapidly broken down in the erythrocyte precursor in the bone marrow [1,2]. Several of these variants are highly unstable and have presented with significant anemia requiring chronic transfusions including Hb Hakkari (HBB: c.95T>G), Hb Chesterfield (HBB: c.86T>G), Hb Terra Haute (HBB: c.320T>G), Hb Cagliari (HBB: c.182T>A) and Hb London-Ontario (HBB: 332T>G) [3][4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

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Hb Calgary (HBB: c.194G>T): A Highly Unstable Hemoglobin Variant with a β-Thalassemia Major Phenotype

Martin

Grimholt

et al. 2021

Hemoglobin

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We describe two unrelated patients, both heterozygous for an unstable hemoglobin (Hb) variant named Hb Calgary (HBB: c.194G>T) that causes severe hemolytic anemia and dyserythropoesis, resulting in transfusion dependence and iron overload. The molecular pathogenesis is a missense variation on the -globin gene, presumed to lead to an unstable Hb. The phenotype of Hb Calgary is particularly severe presenting as transfusion-dependent anemia in early infancy, precluding phenotypic diagnosis and highlighting the importance of early genetic testing in order to make an accurate diagnosis. KEYWORDS Autosomal dominant thalassemia; -globin variant; hemoglobinopathies; inclusion body thalassemia; unstable hemoglobin (Hb)

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hb Calgary (HBB: c.194G>T): A Highly Unstable Hemoglobin Variant with a β-Thalassemia Major Phenotype

Martin

Grimholt

et al. 2021

Hemoglobin

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“…The dominant type mutations could include missense mutations, nonsense mutations or minor insertions or deletions. 8 Examples of a missense mutation causing β-thalassemia intermedia include Hb Terre Haute (β106 Leu → Arg ) , 12 originally described as Hb Indianapolis (β112 Cys → Arg), 13 Hb Chesterfield, 14 Hb Cagliari, 15 Hb Showa-Yakushiji, 16 Hb Durham NC/Brescia, 17 Hb Houston, 18 and more recently, and Hb Mont Saint Aignan. 19 …”

Section: Discussionmentioning

confidence: 99%

Double heterozygosity for hemoglobin C and beta-thalassemia dominant: A rare case of thalassemia intermedia

Agapidou

King

et al. 2018

Hematol Rep

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Beta thalassemia dominant results from mutations in the β globin chain gene resulting in the production of elongated, highly unstable β globin chains. Several such mutations have been described and in a heterozygous state they may confer a phenotype more severe than that of β thalassemia trait and lead to a clinical syndrome of thalassemia intermedia and its associated complications such as extramedullary hemopoiesis, bone disease, endocrinopathies and iron overload even in the absence of transfusion. In this report we present a case of double heterozygosity for HbC and β thalassemia dominant leading to a series of complications that were treated successfully once the correct diagnosis was made.

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“…De novo and autosomal dominantly inherited mutations have been reported in children, usually with a thalassemia intermedia phenotype. In children mutations in exon 2 and 3 occur with approximately equal frequency; one mutation has been reported in exon 1 . Beta chain elongation or alteration of amino acid composition at key positions of the G, B, or H‐helix is hypothesized to alter normal α/β chain interactions.…”

Section: Discussionmentioning

confidence: 99%

Novel dominant β‐thalassemia: Hb Boston‐Kuwait [Codon 139/140(+T)]

Croteau

Luo

Lehmann

et al. 2013

Pediatric Blood & Cancer

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Dominant β-thalassemias exhibit a hybrid phenotype of unstable hemoglobin and ineffective erythropoiesis. Most arise from heterozygous β-globin gene mutations in exons 3 or 2 and present in adulthood as thalassemia intermedia. We report a novel, de novo β-globin mutation presenting in a toddler with features of thalassemia major and chromaturia. Hemoglobin Boston-Kuwait is an elongated β-chain variant (163 amino acids) that results from a frameshift mutation caused by a thymidine insertion in codons 139/140. Hematopoietic stem cell transplant provided a successful alternative therapy for this severe form of dominant β-thalassemia.

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Hemoglobin Chesterfield (beta 28 Leu----Arg) produces the phenotype of inclusion body beta thalassemia [letter]

Cited by 32 publications

References 0 publications

Hb Calgary (HBB: c.194G>T): A Highly Unstable Hemoglobin Variant with a β-Thalassemia Major Phenotype

Hb Calgary (HBB: c.194G>T): A Highly Unstable Hemoglobin Variant with a β-Thalassemia Major Phenotype

Double heterozygosity for hemoglobin C and beta-thalassemia dominant: A rare case of thalassemia intermedia

Novel dominant β‐thalassemia: Hb Boston‐Kuwait [Codon 139/140(+T)]

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