Sickle Cell Disease: From Genetics to Curative Approaches

Sickle cell disease (SCD) is a monogenic blood disease caused by a point mutation in the gene coding for β-globin. The abnormal hemoglobin [sickle hemoglobin (HbS)] polymerizes under low-oxygen conditions and causes red blood cells to sickle. The clinical presentation varies from very severe (with a...

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Bibliographic Details
Published inAnnual review of genomics and human genetics Vol. 24; p. 255
Main Authors Hardouin, Giulia, Magrin, Elisa, Corsia, Alice, Cavazzana, Marina, Miccio, Annarita, Semeraro, Michaela
Format Journal Article
LanguageEnglish
Published Palo Alto Annual Reviews, Inc 01.01.2023
Subjects
Chronic pain
Erythrocytes
Gene therapy
Genetic factors
Hemoglobin
Life span
Point mutation
Sickle cell disease
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Summary:Sickle cell disease (SCD) is a monogenic blood disease caused by a point mutation in the gene coding for β-globin. The abnormal hemoglobin [sickle hemoglobin (HbS)] polymerizes under low-oxygen conditions and causes red blood cells to sickle. The clinical presentation varies from very severe (with acute pain, chronic pain, and early mortality) to normal (few complications and a normal life span). The variability of SCD might be due (in part) to various genetic modulators. First, we review the main genetic factors, polymorphisms, and modifier genes that influence the expression of globin or otherwise modulate the severity of SCD. Considering SCD as a complex, multifactorial disorder is important for the development of appropriate pharmacological and genetic treatments. Second, we review the characteristics, advantages, and disadvantages of the latest advances in gene therapy for SCD, from lentiviral-vector-based approaches to gene-editing strategies.
ISSN:1527-8204
1545-293X
DOI:10.1146/annurev-genom-120122-081037)