RGD Reference Report - POLG1 mutations associated with progressive encephalopathy in childhood. - Rat Genome Database

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POLG1 mutations associated with progressive encephalopathy in childhood.

Authors: Kollberg, G  Moslemi, AR  Darin, N  Nennesmo, I  Bjarnadottir, I  Uvebrant, P  Holme, E  Melberg, A  Tulinius, M  Oldfors, A 
Citation: Kollberg G, etal., J Neuropathol Exp Neurol. 2006 Aug;65(8):758-68.
RGD ID: 8694317
Pubmed: PMID:16896309   (View Abstract at PubMed)
DOI: DOI:10.1097/01.jnen.0000229987.17548.6e   (Journal Full-text)

We have identified compound heterozygous missense mutations in POLG1, encoding the mitochondrial DNA polymerase gamma (Pol gamma), in 7 children with progressive encephalopathy from 5 unrelated families. The clinical features in 6 of the children included psychomotor regression, refractory seizures, stroke-like episodes, hepatopathy, and ataxia compatible with Alpers-Huttenlocher syndrome. Three families harbored a previously reported A467T substitution, which was found in compound with the earlier described G848S or the W748S substitution or a novel R574W substitution. Two families harbored the W748S change in compound with either of 2 novel mutations predicted to give an R232H or M1163R substitution. Muscle morphology showed mitochondrial myopathy with cytochrome c oxidase (COX)-deficient fibers in 4 patients. mtDNA analyses in muscle tissue revealed mtDNA depletion in 3 of the children and mtDNA deletions in the 2 sibling pairs. Neuropathologic investigation in 3 children revealed widespread cortical degeneration with gliosis and subcortical neuronal loss, especially in the thalamus, whereas there were only subcortical neurodegenerative findings in another child. The results support the concept that deletions as well as depletion of mtDNA are involved in the pathogenesis of Alpers-Huttenlocher syndrome and add 3 new POLG1 mutations associated with an early-onset neurodegenerative disease.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Alpers-Huttenlocher syndrome  IAGP 8694317DNA:missense mutations:cds:RGD 
Alpers-Huttenlocher syndrome  ISOPOLG (Homo sapiens)8694317; 8694317DNA:missense mutations:cds:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Polg  (DNA polymerase gamma, catalytic subunit)

Genes (Mus musculus)
Polg  (polymerase (DNA directed), gamma)

Genes (Homo sapiens)
POLG  (DNA polymerase gamma, catalytic subunit)


Additional Information