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Mutations disrupting selenocysteine formation cause progressive cerebello-cerebral atrophy |
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| Authors: | Agamy Orly Ben Zeev Bruria Lev Dorit Marcus Barak Fine Dina Su Dan Narkis Ginat Ofir Rivka Hoffmann Chen Leshinsky-Silver Esther Flusser Hagit Sivan Sara Söll Dieter Lerman-Sagie Tally Birk Ohad S |
| Affiliation: | 1 Morris Kahn Laboratory of Human Genetics, National Institute for Biotechnology in the Negev, Ben Gurion University, Beer-Sheva, Israel 2 Pediatric Neurology Unit and Department of Diagnostic Imaging, Sheba Medical Center, Ramat-Gan, Israel 3 Institute of Medical Genetics and Pediatric Neurology Unit, Wolfson Medical Center, Holon, Israel 4 Departments of Molecular Biophysics and Biochemistry, and Chemistry, Yale University, New Haven, CT, USA 5 Genetics Institute, Soroka University Medical Center, Beer-Sheva, Israel |
| 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. |
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