1. Mutations disrupting selenocysteine formation cause progressive cerebello-cerebral atrophy.
- Author
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Agamy O, Ben Zeev B, Lev D, Marcus B, Fine D, Su D, Narkis G, Ofir R, Hoffmann C, Leshinsky-Silver E, Flusser H, Sivan S, Söll D, Lerman-Sagie T, and Birk OS
- Subjects
- Atrophy genetics, Base Sequence, Chromosome Mapping, Genes, Recessive, Heredodegenerative Disorders, Nervous System pathology, Humans, Iraq ethnology, Molecular Sequence Data, Morocco ethnology, Mutation genetics, Pedigree, Sequence Alignment, Sequence Analysis, DNA, Amino Acyl-tRNA Synthetases genetics, Cerebellum pathology, Cerebral Cortex pathology, Heredodegenerative Disorders, Nervous System genetics, Jews genetics, Selenocysteine biosynthesis
- Abstract
The essential micronutrient selenium is found in proteins as selenocysteine (Sec), the only genetically encoded amino acid whose biosynthesis occurs on its cognate tRNA in humans. In the final step of selenocysteine formation, the essential enzyme SepSecS catalyzes the conversion of Sep-tRNA to Sec-tRNA. We demonstrate that SepSecS mutations cause autosomal-recessive progressive cerebellocerebral atrophy (PCCA) in Jews of Iraqi and Moroccan ancestry. Both founder mutations, common in these two populations, disrupt the sole route to the biosynthesis of the 21st amino acid, Sec, and thus to the generation of selenoproteins in humans., (Copyright © 2010 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)
- Published
- 2010
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