POLG mutations and Alpers syndrome.
Alpers-Huttenlocher syndrome (AHS) an autosomal recessive hepatocerebral syndrome of early onset, has been associated with mitochondrial DNA (mtDNA) depletion and mutations in polymerase gamma gene (POLG). We have identified POLG mutations in four patients with hepatocerebral syndrome and mtDNA depletion in liver, who fulfilled criteria for AHS. All were compound heterozygous for the G848S and W748S mutations, previously reported in patients with progressive external ophtalmoplegia or ataxia. We conclude that AHS should be included in the clinical spectrum of mtDNA depletion and is often associated with POLG mutations, which can cause either multiple mtDNA deletions or mtDNA depletion.
Davidzon
Guido
G
Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Mancuso
Michelangelo
M
Ferraris
Silvio
S
Quinzii
Catarina
C
Hirano
Michio
M
Peters
Heidi L
HL
Kirby
Denise
D
Thorburn
David R
DR
DiMauro
Salvatore
S
D002675:Child, Preschool; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000235:genetics*; D005260:Female; D006501:Hepatic Encephalopathy / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008099:Liver / Q000502:physiology; D008297:Male; D020125:Mutation, Missense
D004272:DNA, Mitochondrial; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human