De novo mutation in POLG leads to haplotype insufficiency and Alpers syndrome.

Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, NC 27709, USA.
Mitochondrion (Impact Factor: 3.52). 06/2009; 9(5):340-5. DOI: 10.1016/j.mito.2009.05.002
Source: PubMed

ABSTRACT Mutations in POLG are a major contributor to pediatric and adult mitochondrial diseases. However, the consequences of many POLG mutations are not well understood. We investigated the molecular cause of Alpers syndome in a patient harboring the POLG mutations A467T in trans with c.2157+5_+6 gc-->ag in intron 12. Analysis of transcripts arising from the c.2157+5_+6 gc-->ag allele revealed alternative splicing with an insertion of 30 intronic nucleotides leading to a premature termination codon. These transcripts were subsequently removed through nonsense-mediated decay, leading to haplotype insufficiency due to expression of the A467T allele and decreased expression of the c.2157+5_+6 gc-->ag allele, which is likely responsible for the Alpers syndrome phenotype.

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