HB Mizuho or α<sub>2</sub>β<sub>2</sub>68(E12)LEU→PRO in a Young Dutch Boy

Harthoorn-Lasthuizen, Else J.; Nabben, F. A. E.; Kazanetz, E. G.; Gu, Li H.; Molchanova, T. P.; Huisman, T. H. J.

doi:10.3109/03630269509036941

Cited by 10 publications

(8 citation statements)

References 3 publications

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“…Mizuho hemoglobinopathy is rare, with only six cases reported, one describes our patient 1–6 . It is characterized by an unstable β chain variant with a Leu➔Pro substitution at position β68 causing disruption of the helical structure and marked hemoglobin instability.…”

Section: Figurementioning

confidence: 90%

“…Mizuho hemoglobinopathy is rare, with only six cases reported, one describes our patient. [1][2][3][4][5][6] It is characterized by an unstable β chain variant with a LeuàPro substitution at position β68 causing disruption of the helical structure and marked hemoglobin instability. We postulate that the rapid clinical decline resulted from acute exacerbation of chronic hemolysis, coupled with severe dehydration, and acidosis secondary to exertional exercise.…”

mentioning

confidence: 99%

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Mizuho hemoglobinopathy, presenting with severe hemolytic anemia and multisystem organ failure secondary to exertion

Sarker

Delvadia

et al. 2021

Transfusion

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Section: Figurementioning

confidence: 90%

mentioning

confidence: 99%

Mizuho hemoglobinopathy, presenting with severe hemolytic anemia and multisystem organ failure secondary to exertion

Sarker

Delvadia

et al. 2021

Transfusion

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“…An excellent example is given in Table IV. Both children with a Hb Mizuho heterozygosity [P68(E12)Leu+Pro] suffer from severe anemia because of the instability of this variant [25,26]. The 2 patients are both 5-year-old males, and their haplotypes are identical except for the nts at -158 ('y), which are TT (haplotypes 3/3) in subject D.C. with 21-22% Hb F and high ' y of 74%, and CC (haplotypes 3A/3A) in subject R.A. with 10% Hb F and low 'Y of 30-3 1 %.…”

Section: Discussionmentioning

confidence: 99%

Variability in the fetal hemoglobin level of the normal adult

et al. 1996

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We analyzed blood samples from more than 200 normal adults, and quantified their Hb F by cation-exchange high-performance liquid chromatography. In several subjects with slightly elevated Hb F (0.4-4.3%), we determined the Ggamma levels in the Hb F and DNA sequence variations in the locus control region II and in the Ggamma and Agamma promoters. About 25% of the approximately 200 normal teenaged high school students had elevated Hb F; detailed analyses of some 20 students, selected at random, identified most as females with a homozygosity for the C-->T variation at position -158 (Ggamma). One 11-year-old boy was heterozygous for the A-->G change at position -161 (Ggamma); he and two of his relatives had approximately 4% Hb F, high Ggamma values, and a high level of (mainly) Ggamma-mRNA. Nearly 40 normal adults from Macedonia and from Georgia (mostly Caucasians) were tentatively identified as Swiss HPFH heterozygotes because slightly elevated Hb F levels were observed at least once. Many of these persons were heterozygous or homozygous for the C-->T mutation at -158 (Ggamma), and a few carried a gamma-globin gene triplication. The C-->T change appears to be an important factor predisposing the adult to increased Hb F production. Evidence suggests a gene dose effect in (mildly) anemic adults; however, other factors besides the C-->T change at -158 (Ggamma), including factors not linked to the beta-globin region, may cause an increase in gamma-chain synthesis.

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“…Hb Mizuho is a severely unstable Hb variant. It has been found four times in patients who presented with severe hemolytic anemia, and all instances were believed to be de novo mutations [13][14][15]. The instability of this variant is due to the introduction of a proline residue in helix E, which disrupts the alpha helix and decreases its ability to bind the heme group.…”

Section: Discussionmentioning

confidence: 99%

“…The adjacent valine (E11) is a heme binding site, so mutations at this site might be expected to result in altered oxygen affinity. Three different mutations have been described at b68: Hb Mizuho (b68 Leu?Pro) [13][14][15], Hb Brisbane (also known as Hb Great Lakes) (b68 Leu?Phe) [16][17][18], and Hb Loves Park. Hb Jamaica Plain [4] is a doubly substituted variant that contains the Hb Loves Park substitution.…”

Section: Discussionmentioning

confidence: 99%

Hemoglobin Loves Park [β68 (E12) Leu→Phe]: Report of five cases including one originating from a de novo mutation

et al. 2006

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Hemoglobin (Hb) Loves Park [b68 (E12) Leu?Phe] was identified in a 2-year-old Portuguese boy with anemia, microcytosis, and hypochromia. This Hb variant was detected by isoelectric focusing and quantified by reverse-phase high-performance liquid chromatography (HPLC) (48.4%), and the DNA mutation was identified by HBB (b-globin gene) sequencing. Hematological and biochemical analyses performed on his parents revealed normal hematological parameters and normal hemoglobin and globin chain profiles. DNA sequence analysis of the HBB gene of both parents showed the absence of the Hb Loves Park mutation. Study of the haplotypes in the b-globin gene cluster confirmed parenthood. Moreover, paternity was confirmed by the study of nine short tandem repeats (STRs) and four variable-number tandem repeat (VNTRs) loci. The most likely explanation for these results is that the Hb Loves Park mutation has occurred de novo in this family. The original American cases of Hb Loves Park, from a family of Italian origin, which were never published, as well as two additional cases, are also included in this report. Functional studies revealed that Hb Loves Park is stable and has a decreased oxygen affinity. Am. J. Hematol. 81:256-261, 2006. V V C 2006 Wiley-Liss, Inc.

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HB Mizuho or α₂β₂68(E12)LEU→PRO in a Young Dutch Boy

Cited by 10 publications

References 3 publications

Mizuho hemoglobinopathy, presenting with severe hemolytic anemia and multisystem organ failure secondary to exertion

Mizuho hemoglobinopathy, presenting with severe hemolytic anemia and multisystem organ failure secondary to exertion

Variability in the fetal hemoglobin level of the normal adult

Hemoglobin Loves Park [β68 (E12) Leu→Phe]: Report of five cases including one originating from a de novo mutation

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HB Mizuho or α2β268(E12)LEU→PRO in a Young Dutch Boy

Cited by 10 publications

References 3 publications

Mizuho hemoglobinopathy, presenting with severe hemolytic anemia and multisystem organ failure secondary to exertion

Mizuho hemoglobinopathy, presenting with severe hemolytic anemia and multisystem organ failure secondary to exertion

Variability in the fetal hemoglobin level of the normal adult

Hemoglobin Loves Park [β68 (E12) Leu→Phe]: Report of five cases including one originating from a de novo mutation

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HB Mizuho or α₂β₂68(E12)LEU→PRO in a Young Dutch Boy