Genetic Variation and Sickle Cell Disease Severity: A Systematic Review and Meta-Analysis.
Justin K Kirkham et al. JAMA Netw Open 2023 10 (10) e2337484
From the abstract: " What genetic modifiers of sickle cell disease (SCD) are currently defined, and what are potential approaches to improve future studies?
In this systematic review and meta-analysis of 571 studies examining 29?670 individuals with SCD, 17?757 associations involving 1552 genes and 25 SCD phenotype categories were discovered; of these, only 173 associations met the study design, reporting, and phenotype or genotype harmonization required for meta-analysis. Gene variants regulating fetal hemoglobin and a-thalassemia were frequently identified, but other associations remained unconfirmed."
Potent and uniform fetal hemoglobin induction via base editing.
Thiyagaraj Mayuranathan et al. Nat Genet 2023 7
Inducing fetal hemoglobin (HbF) in red blood cells can alleviate ß-thalassemia and sickle cell disease. We compared five strategies in CD34+ hematopoietic stem and progenitor cells, using either Cas9 nuclease or adenine base editors. The most potent modification was adenine base editor generation of ?-globin –175A>G. Homozygous –175A>G edited erythroid colonies expressed 81?±?7% HbF versus 17?±?11% in unedited controls, whereas HbF levels were lower and more variable for two Cas9 strategies targeting a BCL11A binding motif in the ?-globin promoter or a BCL11A erythroid enhancer.
The beta thalassaemia trait in Jamaica
JR Sergeant et al, J comm Genetics, June 30, 2023
The objective of this study was to review the prevalence and features of the beta thalassaemia trait in Jamaican populations. Screening of 221,306 newborns over the last 46 years has given an indication of the distribution and prevalence of beta thalassaemia genes, and screening of 16,612 senior school students in Manchester parish, central Jamaica, has provided their haematological features. The prevalence of the beta thalassaemia trait predicted from double heterozygotes was 0.8% of 100,000 babies in Kingston, 0.9% of 121,306 newborns in southwest Jamaica, and 0.9% of school students in Manchester.
CRISPR Therapy Exceeds Targets in Thalassemia, Sickle Cell Disease
M Basset, Medpage today, June 13, 2023
Data from two pivotal trials suggest that a single infusion of the CRISPR-based gene therapy exagamglogene autotemcel (exa-cel) can provide a "functional cure" for patients with transfusion-dependent beta-thalassemia or severe sickle cell disease.