Children with HbSβ<sup>0</sup> thalassemia have higher hemoglobin levels and lower incidence rate of acute chest syndrome compared to children with HbSS

Day, Melissa E.; Rodeghier, Mark; DeBaun, Michael R.

doi:10.1002/pbc.27352

Cited by 10 publications

(6 citation statements)

References 12 publications

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“…These findings are largely consistent with a prior study of HbSβ 0 (n = 22) and HbSS (n = 786) pediatric patients, which included genotyping whereby a lower intracranial TCD velocity was observed in HbSβ 0 vs HbSS participants, but with no significant impact on infarct prevalence. 4 Certain individuals with intracranial stenosis would be expected to have elevated TCD velocities and as such this prior work is consistent with no patients here with HbSβ 0 having vasculopathy.…”

supporting

confidence: 82%

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Cerebral hemodynamics and metabolism are similar in sickle cell disease patients with hemoglobin SS and Sβ⁰ thalassemia phenotypes

et al. 2019

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supporting

confidence: 82%

“…Yet the prevalence of cerebral infarcts was not statistically different for HbSβ 0 (27.8%) vs HbSS (30.8%) individuals. 4 These data collectively suggest that some hematological differences in phenotype may not manifest as tissue injury.…”

mentioning

confidence: 93%

Cerebral hemodynamics and metabolism are similar in sickle cell disease patients with hemoglobin SS and Sβ⁰ thalassemia phenotypes

et al. 2019

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“…power to compare VOP event rate and occurrence between patients with HbSS and those with HbSb 0 -thalassemia, and no difference was observed in a prior study. 40 Therefore, we combined the genotypes for both groups of participants for the current analysis. Most participants (91.4%-81%) had no VOP events across each year of life, whereas 5.2% to 8.8% had 1 VOP event per year.…”

Section: Genetic Modifiers Of Rbc %Hbfmentioning

confidence: 99%

A polygenic score for acute vaso-occlusive pain in pediatric sickle cell disease

Rampersaud¹,

Kang

Palmer³

et al. 2021

Blood Advances

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Individuals with monogenic disorders can experience variable phenotypes that are influenced by genetic variation. To investigate this in sickle cell disease (SCD), we performed whole-genome sequencing (WGS) of 722 individuals with hemoglobin HbSS or HbSβ0-thalassemia from Baylor College of Medicine and from the St. Jude Children’s Research Hospital Sickle Cell Clinical Research and Intervention Program (SCCRIP) longitudinal cohort study. We developed pipelines to identify genetic variants that modulate sickle hemoglobin polymerization in red blood cells and combined these with pain-associated variants to build a polygenic score (PGS) for acute vaso-occlusive pain (VOP). Overall, we interrogated the α-thalassemia deletion −α3.7 and 133 candidate single-nucleotide polymorphisms (SNPs) across 66 genes for associations with VOP in 327 SCCRIP participants followed longitudinally over 6 years. Twenty-one SNPs in 9 loci were associated with VOP, including 3 (BCL11A, MYB, and the β-like globin gene cluster) that regulate erythrocyte fetal hemoglobin (HbF) levels and 6 (COMT, TBC1D1, KCNJ6, FAAH, NR3C1, and IL1A) that were associated previously with various pain syndromes. An unweighted PGS integrating all 21 SNPs was associated with the VOP event rate (estimate, 0.35; standard error, 0.04; P = 5.9 × 10−14) and VOP event occurrence (estimate, 0.42; standard error, 0.06; P = 4.1 × 10−13). These associations were stronger than those of any single locus. Our findings provide insights into the genetic modulation of VOP in children with SCD. More generally, we demonstrate the utility of WGS for investigating genetic contributions to the variable expression of SCD-associated morbidities.

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“…The clinical features of HbS + -thal and HbSC are generally less severe than those in SCA [18]. HbS 0 -thal is generally considered clinically indistinguishable from SCA, although some studies have reported a slightly lower incidence of SCD comorbidities [19].…”

Section: Hemoglobin Disordersmentioning

confidence: 99%

Innovative Therapies for Hemoglobin Disorders

Sii-Felice¹,

Nègre²,

Brendel³

et al. 2020

BioDrugs

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-globin gene transfer has been used as a paradigm for hematopoietic stem cell (HSC) gene therapy, but is subject to major difficulties, such as the lack of selection of genetically corrected HSCs, the need for high-level expression of the therapeutic gene, and cell-specific transgene expression. It took more than 40 years for scientists and physicians to advance from the cloning of globin gene and discovering globin gene mutations to improving our understanding of the pathophysiological mechanisms involved, the detection of genetic modifiers, the development of animal models and gene transfer vectors, comprehensive animal testing, and demonstrations of phenotypic improvement in clinical trials, culminating in the authorization of the first gene therapy product for -thalassemia in 2019. Research has focused mostly on the development of lentiviral gene therapy vectors expressing variants of the -globin gene, or more recently targeting a -globin repressor, some of which have entered clinical testing and should soon diversify the available treatments and promote price competition. These results are encouraging, but we have yet to reach the end of the story. New molecular and cellular tools, such as gene editing or the development of induced pluripotent stem cells, are being developed, heralding the emergence of alternative products, the efficacy and safety of which are being studied. Hemoglobin disorders constitute an important model for testing the pros and cons of these advanced technologies, some of which are already in the clinical phase. In this review, we focus on the development of the advanced products, and recent technological innovations which could lead to clinical trials in the near future, and provide hope for a definitive cure of these severe conditions.

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Children with HbSβ⁰ thalassemia have higher hemoglobin levels and lower incidence rate of acute chest syndrome compared to children with HbSS

Cited by 10 publications

References 12 publications

Cerebral hemodynamics and metabolism are similar in sickle cell disease patients with hemoglobin SS and Sβ⁰ thalassemia phenotypes

Cerebral hemodynamics and metabolism are similar in sickle cell disease patients with hemoglobin SS and Sβ⁰ thalassemia phenotypes

A polygenic score for acute vaso-occlusive pain in pediatric sickle cell disease

Innovative Therapies for Hemoglobin Disorders

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Children with HbSβ0 thalassemia have higher hemoglobin levels and lower incidence rate of acute chest syndrome compared to children with HbSS

Cited by 10 publications

References 12 publications

Cerebral hemodynamics and metabolism are similar in sickle cell disease patients with hemoglobin SS and Sβ0 thalassemia phenotypes

Cerebral hemodynamics and metabolism are similar in sickle cell disease patients with hemoglobin SS and Sβ0 thalassemia phenotypes

A polygenic score for acute vaso-occlusive pain in pediatric sickle cell disease

Innovative Therapies for Hemoglobin Disorders

Contact Info

Product

Resources

About

Children with HbSβ⁰ thalassemia have higher hemoglobin levels and lower incidence rate of acute chest syndrome compared to children with HbSS

Cerebral hemodynamics and metabolism are similar in sickle cell disease patients with hemoglobin SS and Sβ⁰ thalassemia phenotypes

Cerebral hemodynamics and metabolism are similar in sickle cell disease patients with hemoglobin SS and Sβ⁰ thalassemia phenotypes