POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion

Authors

  • Robert K. Naviaux MD, PhD,

    Corresponding author
    1. Departments of Medicine, University of California, San Diego School of Medicine, San Diego, CA
    2. Departments of Pediatrics, University of California, San Diego School of Medicine, San Diego, CA
    3. The Mitochondrial and Metabolic Disease Center, University of California, San Diego School of Medicine, San Diego, CA
    • Departments of Medicine and Pediatrics and the Mitochondrial and Metabolic Disease Center, University of California, San Diego School of Medicine, 214 Dickinson Street, Building CTF, Room C-103, San Diego, CA 92103-8467
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  • Khue V. Nguyen PhD

    1. Departments of Medicine, University of California, San Diego School of Medicine, San Diego, CA
    2. The Mitochondrial and Metabolic Disease Center, University of California, San Diego School of Medicine, San Diego, CA
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Abstract

Alpers' syndrome is a fatal neurogenetic disorder first described more than 70 years ago. It is an autosomal recessive, developmental mitochondrial DNA depletion disorder characterized by deficiency in mitochondrial DNA polymerase γ (POLG) catalytic activity, refractory seizures, neurodegeneration, and liver disease. In two unrelated pedigrees of Alpers' syndrome, each affected child was found to carry a homozygous mutation in exon 17 of the POLG locus that led to a Glu873Stop mutation just upstream of the polymerase domain of the protein. In addition, each affected child was heterozygous for the G1681A mutation in exon 7 that led to an Ala467Thr substitution in POLG, within the linker region of the protein. Ann Neurol 2004

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