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POLG1 mutations ass...
POLG1 mutations associated with progressive encephalopathy in childhood.
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- Kollberg, Gittan, 1963 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology
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- Moslemi, Ali-Reza (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology
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- Darin, Niklas, 1964 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
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- Nennesmo, Inger (author)
- Karolinska Institutet
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- Bjarnadottir, Ingibjörg (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
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- Uvebrant, Paul, 1951 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
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- Holme, Elisabeth, 1947 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
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- Melberg, Atle (author)
- Uppsala universitet,Institutionen för neurovetenskap
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- Tulinius, Mar, 1953 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
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- Oldfors, Anders, 1951 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology
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(creator_code:org_t)
- 2006-08-01
- 2006
- English.
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In: Journal of neuropathology and experimental neurology. - : Oxford University Press (OUP). - 0022-3069 .- 1554-6578. ; 65:8, s. 758-68
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Abstract
Subject headings
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- 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.
Keyword
- Adolescent
- Age of Onset
- Brain
- metabolism
- pathology
- physiopathology
- Child
- Preschool
- Conserved Sequence
- genetics
- DNA Mutational Analysis
- DNA
- Mitochondrial
- biosynthesis
- genetics
- DNA-Directed DNA Polymerase
- genetics
- Diffuse Cerebral Sclerosis of Schilder
- genetics
- metabolism
- physiopathology
- Electron Transport Complex IV
- genetics
- metabolism
- Fatal Outcome
- Female
- Genetic Predisposition to Disease
- genetics
- Genetic Screening
- Humans
- Infant
- Liver Diseases
- genetics
- pathology
- physiopathology
- Male
- Mitochondria
- genetics
- metabolism
- pathology
- Mitochondrial Diseases
- genetics
- metabolism
- physiopathology
- Mitochondrial Myopathies
- genetics
- metabolism
- physiopathology
- Muscle
- Skeletal
- metabolism
- pathology
- physiopathology
- Mutation
- Missense
- genetics
- Pedigree
- Syndrome
- Alpers-Huttenlocher syndrome
- MEDICINE
Publication and Content Type
- ref (subject category)
- art (subject category)
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Kollberg, Gittan ...
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Moslemi, Ali-Rez ...
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Darin, Niklas, 1 ...
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Nennesmo, Inger
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Bjarnadottir, In ...
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Uvebrant, Paul, ...
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Holme, Elisabeth ...
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Melberg, Atle
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Tulinius, Mar, 1 ...
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Oldfors, Anders, ...
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- Articles in the publication
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Journal of neuro ...
- By the university
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University of Gothenburg
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Uppsala University
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Karolinska Institutet