FOUR NEW VARIANTS OF THEα2-GLOBIN GENE WITHOUT CLINICAL OR HEMATOLOGIC EFFECTS: Hb PARK RIDGE [α9(A7)Asn→Lys (α2)], Hb NORTON [α72(EF1)His→Asp (α2)], HbLOMBARD [α103(G10)His→Tyr (α2)], AND Hb SAN ANTONIO [α113(GH2)Leu→Arg (α2)]

Hoyer, James D.; McCormick, Daniel J.; Snow, Karen; Kwon, Jong Hwa; Booth, David R.; Duarte, Manuel; Grayson, Guy H.; Kubik, Kathleen S.; Holmes, Michael W.R.; Fairbanks, Virgil F.

doi:10.1081/hem-120005456

Cited by 6 publications

(1 citation statement)

References 16 publications

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“…Nevertheless, clinical silence has been reported in heterozygotes [ 18 ]. Different mutations occur on codon 9 of the α2-globin gene in Hb Park Ridge [α2 9(A7) Asn > Lys, HBA2:c.30C > G] and Hb Zurich-Hottingen [α2 9(A7) Asn > Ser HBA2:c.29A > G] [ 26 , 27 ]. Both variants show no functional abnormality or instability, and they are associated with normal hematological values.…”

Section: Discussionmentioning

confidence: 99%

Hemoglobin profile and molecular characteristics of the complex interaction of hemoglobin Doi-Saket [α9(A7) asn > lys, HBA2:c.30C > a], a novel α2α1 hybrid globin variant, with hemoglobin E [β26(B8) Glu > lys, HBB:c.79G > A] and deletional α ⁺ -thalassemia in a Thai family

Panyasai,

Khongthai,

Satthakarn

2023

Annals of Medicine

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Background An increasing number of α-hemoglobin (Hb) variants is causing various clinical symptoms; therefore, accurate identification of these Hb variants is important. Objective This study aimed to describe the molecular and hematological characteristics of novel Hb Doi-Saket that gives rise to a typical α + -thalassemia phenotype in carriers with and without other hemoglobinopathies. Materials and Methods Biological samples from a proband and his family members were analyzed. Hematological profiles were analyzed using a standard automated cell counter. Hb was analyzed by capillary electrophoresis and high-performance liquid chromatography. Mutations and globin haplotype were identified by DNA analysis. Novel diagnostic tools based on allele-specific polymerase chain reaction (PCR) and PCR–restriction fragment length polymorphism were developed. Results Hb analysis showed a major abnormal Hb fraction, moving slower than HbA, and a minor Hb fraction alongside HbA 2 in the proband, his father, and son. DNA analysis of the α-globin gene identified the -α 3.7 deletion and in cis the C > A mutation on codon 9 of the α2α1 gene, corresponding to Hb Doi-Saket [α9(A7) Asn > Lys]. This mutation could be identified using newly developed allele-specific PCR-based assays. The Hb Doi-Saket al.lele was significantly associated with haplotype [- + M + + 0 -]. Interaction of α Doi-Saket with β E globin chains led to a new Hb variant (HbE Doi-Saket). Phenotypic expression was clinically silent in heterozygotes and might present slight microcytosis. Conclusions Hb Doi-Saket emphasizes a great diversity present in α-globin gene. The mutation in this family from Thailand was linked to -α 3.7 and caused mild microcytosis in the carriers. The combination of this variant with deletions in α genes might cause a severe clinical phenotype. Different methods of separation can provide useful information in diagnosis, and a complete molecular approach is needed for confirmation before considering patient management.

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Section: Discussionmentioning

confidence: 99%

Hemoglobin profile and molecular characteristics of the complex interaction of hemoglobin Doi-Saket [α9(A7) asn > lys, HBA2:c.30C > a], a novel α2α1 hybrid globin variant, with hemoglobin E [β26(B8) Glu > lys, HBB:c.79G > A] and deletional α ⁺ -thalassemia in a Thai family

Panyasai,

Khongthai,

Satthakarn

2023

Annals of Medicine

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Impaired binding of AHSP to α chain variants: Hb Groene Hart illustrates a mechanism leading to unstable hemoglobins with α thalassemic like syndrome

Vasseur

Marden

Giordano³

et al. 2006

Blood Cells, Molecules, and Diseases

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In SilicoAnalysis of the Effects of Point Mutations on α-Globin: Implications for α-Thalassemia

Horri-Naceur

Timson

2020

Hemoglobin

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FOUR NEW VARIANTS OF THEα2-GLOBIN GENE WITHOUT CLINICAL OR HEMATOLOGIC EFFECTS: Hb PARK RIDGE [α9(A7)Asn→Lys (α2)], Hb NORTON [α72(EF1)His→Asp (α2)], HbLOMBARD [α103(G10)His→Tyr (α2)], AND Hb SAN ANTONIO [α113(GH2)Leu→Arg (α2)]

Cited by 6 publications

References 16 publications

Hemoglobin profile and molecular characteristics of the complex interaction of hemoglobin Doi-Saket [α9(A7) asn > lys, HBA2:c.30C > a], a novel α2α1 hybrid globin variant, with hemoglobin E [β26(B8) Glu > lys, HBB:c.79G > A] and deletional α ⁺ -thalassemia in a Thai family

Hemoglobin profile and molecular characteristics of the complex interaction of hemoglobin Doi-Saket [α9(A7) asn > lys, HBA2:c.30C > a], a novel α2α1 hybrid globin variant, with hemoglobin E [β26(B8) Glu > lys, HBB:c.79G > A] and deletional α ⁺ -thalassemia in a Thai family

Impaired binding of AHSP to α chain variants: Hb Groene Hart illustrates a mechanism leading to unstable hemoglobins with α thalassemic like syndrome

In SilicoAnalysis of the Effects of Point Mutations on α-Globin: Implications for α-Thalassemia

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FOUR NEW VARIANTS OF THEα2-GLOBIN GENE WITHOUT CLINICAL OR HEMATOLOGIC EFFECTS: Hb PARK RIDGE [α9(A7)Asn→Lys (α2)], Hb NORTON [α72(EF1)His→Asp (α2)], HbLOMBARD [α103(G10)His→Tyr (α2)], AND Hb SAN ANTONIO [α113(GH2)Leu→Arg (α2)]

Cited by 6 publications

References 16 publications

Hemoglobin profile and molecular characteristics of the complex interaction of hemoglobin Doi-Saket [α9(A7) asn > lys, HBA2:c.30C > a], a novel α2α1 hybrid globin variant, with hemoglobin E [β26(B8) Glu > lys, HBB:c.79G > A] and deletional α + -thalassemia in a Thai family

Hemoglobin profile and molecular characteristics of the complex interaction of hemoglobin Doi-Saket [α9(A7) asn > lys, HBA2:c.30C > a], a novel α2α1 hybrid globin variant, with hemoglobin E [β26(B8) Glu > lys, HBB:c.79G > A] and deletional α + -thalassemia in a Thai family

Impaired binding of AHSP to α chain variants: Hb Groene Hart illustrates a mechanism leading to unstable hemoglobins with α thalassemic like syndrome

In SilicoAnalysis of the Effects of Point Mutations on α-Globin: Implications for α-Thalassemia

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Hemoglobin profile and molecular characteristics of the complex interaction of hemoglobin Doi-Saket [α9(A7) asn > lys, HBA2:c.30C > a], a novel α2α1 hybrid globin variant, with hemoglobin E [β26(B8) Glu > lys, HBB:c.79G > A] and deletional α ⁺ -thalassemia in a Thai family

Hemoglobin profile and molecular characteristics of the complex interaction of hemoglobin Doi-Saket [α9(A7) asn > lys, HBA2:c.30C > a], a novel α2α1 hybrid globin variant, with hemoglobin E [β26(B8) Glu > lys, HBB:c.79G > A] and deletional α ⁺ -thalassemia in a Thai family