In a patient with autosomal recessive PEO (PEOB1; 258450), Lamantea et al. (2002) identified compound heterozygosity for 2 mutations in the POLG gene: gly848-to-ser (G848S) and thr251-to-ile (T251I; 174763.0007).
In a patient with PEO, Van Goethem et al. (2003) identified a heterozygous G848S mutation in the POLG gene and a heterozygous arg334-to-gln mutation in the C10ORF2 gene (R334Q; 606075.0008), indicating a digenic mode of inheritance.
In 4 children with mitochondrial DNA depletion syndrome-4A (MTDPS4A; 203700), manifest as Alpers syndrome, Davidzon et al. (2005) identified compound heterozygosity for 2 mutations in the POLG gene: G848S and W748S (174763.0013). All patients died in childhood. Davidzon et al. (2005) noted that the G848S mutation occurs within the polymerase motif C of the enzyme.
Nguyen et al. (2005) reported 2 unrelated patients with mtDNA depletion syndrome-4A, manifest as Alpers syndrome. One was compound heterozygous for G848S and A467T (174763.0002), and the other was compound heterozygous for G848S and W748S.
Hakonen et al. (2007) presented evidence that the G848S disease chromosome originated from a common founder, possibly of European origin.
In an infant with mtDNA depletion syndrome-4B (MTDPS4B; 613662), manifest as severe hypotonia and gastrointestinal dysmotility (MNGIE), Giordano et al. (2009) identified compound heterozygosity for 2 mutations in the POLG gene: G848S and a 697C-T transition, resulting in an arg227-to-trp (R227W; 174763.0021) substitution. Other features included hearing loss and clubfoot. Brain MRI showed enlarged ventricles, but leukoencephalopathy was not noted. There was no liver damage aside from that resulting from parenteral nutrition. Analysis of the bowel showed that mtDNA depletion was mainly confined to the external layer of the muscularis propria.
