1. Genetic diseases of the Kennedy pathways for membrane synthesis.
- Author
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Tavasoli M, Lahire S, Reid T, Brodovsky M, and McMaster CR
- Subjects
- Animals, Choline Kinase chemistry, Choline Kinase genetics, Choline-Phosphate Cytidylyltransferase chemistry, Choline-Phosphate Cytidylyltransferase genetics, Cytidine Diphosphate metabolism, Genetic Association Studies, Humans, Muscular Dystrophies congenital, Muscular Dystrophies genetics, Muscular Dystrophies pathology, Osteochondrodysplasias congenital, Osteochondrodysplasias genetics, Osteochondrodysplasias pathology, Polymorphism, Single Nucleotide, Cytidine Diphosphate analogs & derivatives, Cytidine Diphosphate Choline metabolism, Ethanolamines metabolism
- Abstract
The two branches of the Kennedy pathways (CDP-choline and CDP-ethanolamine) are the predominant pathways responsible for the synthesis of the most abundant phospholipids, phosphatidylcholine and phosphatidylethanolamine, respectively, in mammalian membranes. Recently, hereditary diseases associated with single gene mutations in the Kennedy pathways have been identified. Interestingly, genetic diseases within the same pathway vary greatly, ranging from muscular dystrophy to spastic paraplegia to a childhood blinding disorder to bone deformations. Indeed, different point mutations in the same gene (PCYT1; CCTα) result in at least three distinct diseases. In this review, we will summarize and review the genetic diseases associated with mutations in genes of the Kennedy pathway for phospholipid synthesis. These single-gene disorders provide insight, indeed direct genotype-phenotype relationships, into the biological functions of specific enzymes of the Kennedy pathway. We discuss potential mechanisms of how mutations within the same pathway can cause disparate disease., (Copyright © 2020 © 2020 Tavasoli et al. Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2020
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