Mutations disrupting selenocysteine formation cause progressive cerebello-cerebral atrophy

Orly Agamy, Bruria Ben Zeev, Dorit Lev, Barak Marcus, Dina Fine, Dan Su, Ginat Narkis, Rivka Ofir, Chen Hoffmann, Esther Leshinsky-Silver, Hagit Flusser, Sara Sivan, Dieter Söll, Tally Lerman-Sagie, Ohad S. Birk

Research output: Contribution to journalArticlepeer-review

123 Scopus citations

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.

Original languageEnglish
Pages (from-to)538-544
Number of pages7
JournalAmerican Journal of Human Genetics
Volume87
Issue number4
DOIs
StatePublished - 8 Oct 2010

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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