Hereditary persistence of fetal hemoglobin (HPFH) is a benign condition in which significant fetal hemoglobin production continues well into adulthood, disregarding the normal shutoff point after which only adult-type hemoglobin should be produced. The percentage of incorrect expression might be as low as 10%-15% or as high as 100% of the total hemoglobin, usually higher in homozygotes than in heterozygotes. The present case is a typical example of homozygous HPFH.
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http://dx.doi.org/10.4103/ajts.AJTS_71_16 | DOI Listing |
J Pediatr Surg
December 2024
Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:
Background: We sought to determine whether transamniotic stem cell therapy (TRASCET) could be a viable alternative for the fetal administration of genetically modified hematopoietic stem cells (HSCs) carrying a human hemoglobin subunit beta gene (hHBB) in a healthy syngeneic rat model.
Methods: Time-dated pregnant Lewis dams underwent volume-matched intra-amniotic injections in all their fetuses (n = 61) of a suspension of donor HSCs genetically modified with either both a hHBB gene and a firefly luciferase reporter gene (n = 42) or the firefly luciferase reporter gene alone to control for HBB-derived protein interspecies homology (n = 19) on gestational day 17 (E17; term = E21). Donor HSCs consisted of syngeneic cells phenotyped by flow cytometry with successful hHBB transduction confirmed by ELISA prior to administration in vivo.
Adv Sci (Weinh)
December 2024
Innovation Center for Diagnostics and Treatment of Thalassemia, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Despite the well-documented mutation spectra of β-thalassemia, the genetic variants and haplotypes of globin gene clusters modulating its clinical heterogeneity remain incompletely illustrated. Here, a targeted long-read sequencing (T-LRS) is demonstrated to capture 20 genes/loci in 1,020 β-thalassemia patients. This panel permits not only identification of thalassemia mutations at 100% of sensitivity and specificity, but also detection of rare structural variants (SVs) and single nucleotide variants (SNVs) in modifier genes/loci.
View Article and Find Full Text PDFStem Cell Res Ther
December 2024
Centre for Stem Cell Research (CSCR), A Unit of InStem Bengaluru, Christian Medical College Campus, Vellore, Tamil Nadu, 632002, India.
Background: Sickle cell disease (SCD) and β-thalassemia patients with elevated gamma globin (HBG1/G2) levels exhibit mild or no symptoms. To recapitulate this natural phenomenon, the most coveted gene therapy approach is to edit the regulatory sequences of HBG1/G2 to reactivate them. By editing more than one regulatory sequence in the HBG promoter, the production of fetal hemoglobin (HbF) can be significantly increased.
View Article and Find Full Text PDFInt J Lab Hematol
December 2024
Department of Hematology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Background: δβ-thalassemia/HPFH is an uncommon hemoglobinopathy characterized by decreased or the total absence of production of δ- and β-globin and increased HbF levels. Both these disorders have variable genotype and phenotype, but significant overlap in the clinical and laboratory findings. Given the lack of literature in this regard, the study aimed to estimate the prevalence of the disease and evaluate its clinical, hematological, and molecular profile in India.
View Article and Find Full Text PDFCytotherapy
December 2024
Molecular and Clinical Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.
Sickle cell disease (SCD) is the most common inherited blood disorder worldwide, impacting millions and imposing severe healthcare challenges, particularly in resource-limited regions. Current treatments have variable efficacy and require lifelong adherence. Allogeneic Hematopoietic Stem Cell Transplantation can be curative but comes with significant side effects and limited donor availability limits its widespread applicability.
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