RGD Reference Report - A novel POLG gene mutation in 4 children with Alpers-like hepatocerebral syndromes. - Rat Genome Database

Send us a Message
Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   
Search RGD Grant Resources Citing RGD About Us Contact Us
Genes Variants Community Projects QTLs Strains Markers Genome Information Ontologies Cell Lines References Download Submit Data
OntoMate (Literature Search) JBrowse (Genome Browser) Synteny Browser (VCMap) Variant Visualizer Multi-Ontology Enrichment (MOET) Gene-Ortholog Location Finder (GOLF) InterViewer (Protein-Protein Interactions) PhenoMiner (Quatitative Phenotypes) Gene Annotator OLGA (Gene List Generator) AllianceMine GViewer (Genome Viewer)
Aging & Age-Related Disease Cancer & Neoplastic Disease Cardiovascular Disease Coronavirus Disease Developmental Disease Diabetes Hematologic Disease Immune & Inflammatory Disease Infectious Disease Liver Disease Neurological Disease Obesity & Metabolic Syndrome Renal Disease Respiratory Disease Sensory Organ Disease
Find Models Genetic Models Autism Models Rat PhenoMiner (Quantitative Phenotypes) Chinchilla PhenoMiner Expected Ranges (Quantitative Phenotype) PhenoMiner Term Comparison Hybrid Rat Diversity Panel Phenotypes Phenotypes in Other Animal Models Animal Husbandry Strain Medical Records Phylogenetics Strain Availability Calendar Rats 101 Submissions Photo Archive
Pathways
Rat Community Forum Directory of Rat Laboratories Video Tutorials News RGD Publications RGD Presentations Archive Nomenclature Guidelines Resource Links Laboratory Resources Employment Resources
Advanced Search (OLGA)

A novel POLG gene mutation in 4 children with Alpers-like hepatocerebral syndromes.

Authors: Kurt, Bulent  Jaeken, Jaak  Van Hove, Johan  Lagae, Lieven  Löfgren, Ann  Everman, David B  Jayakar, Parul  Naini, Ali  Wierenga, Klaas J  Van Goethem, Gert  Copeland, William C  DiMauro, Salvatore 
Citation: Kurt B, etal., Arch Neurol. 2010 Feb;67(2):239-44. doi: 10.1001/archneurol.2009.332.
RGD ID: 15039298
Pubmed: PMID:20142534   (View Abstract at PubMed)
PMCID: PMC3826985   (View Article at PubMed Central)
DOI: DOI:10.1001/archneurol.2009.332   (Journal Full-text)


OBJECTIVE: To describe a novel POLG missense mutation (c.3218C>T; p.P1073L) that, in association with 2 previously described mutations, caused an Alpers-like hepatocerebral syndrome in 4 children.
DESIGN: Genotype-phenotype correlation.
SETTING: Tertiary care universities.
PATIENTS: Four children, 2 related and 2 unrelated, with the novel p.P1073L mutation (all patients) and either the p.A467T (2 patients), p.G848S (1 patient), or p.W748S (1 patient) mutation presented with psychomotor delay, encephalopathy, and liver failure.
INTERVENTIONS: Detailed clinical and laboratory examinations including brain magnetic resonance imaging, muscle biopsy, measurement of mitochondrial DNA, and sequencing of the POLG gene.
MAIN OUTCOME MEASURES: Definition of clinical variability.
RESULTS: All 4 patients had psychomotor delay, seizures, and liver disease. Three patients had severe gastrointestinal dysmotility, which may be associated with the new p.P1073L mutation.
CONCLUSIONS: The heterozygous presence of the novel p.P1073L mutation in trans with another recessive POLG mutation causes a hepatocerebral disorder identical or very similar to Alpers syndrome. This adds to the already striking clinical heterogeneity of POLG mutations. In the Belgian patients, the familial occurrence without consanguinity is related to the high frequency of the recessive p.A467T and p.W748S mutations in northwestern Europe and reveals a pitfall for diagnosis and genetic counseling.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
POLGHumanAlpers-Huttenlocher syndrome susceptibilityIAGP DNA:missense mutation:cds:p.P1073L (3218C>T) (human)RGD 
PolgRatAlpers-Huttenlocher syndrome susceptibilityIAGP DNA:missense mutation:cds:p.P1073L (3218C>T) (human)RGD 
PolgMouseAlpers-Huttenlocher syndrome susceptibilityIAGP DNA:missense mutation:cds:p.P1073L (3218C>T) (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
POLGHumanAbnormality of the liver susceptibilityIAGP DNA:missense mutation:cds:p.P1073L (3218C>T)RGD 
POLGHumanGastrointestinal dysmotility susceptibilityIAGP DNA:missense mutation:cds:p.P1073L (3218C>T)RGD 
POLGHumanGlobal developmental delay susceptibilityIAGP DNA:missense mutation:cds:p.P1073L (3218C>T)RGD 
POLGHumanLactic acidosis susceptibilityIAGP DNA:missense mutation:cds:p.P1073L (3218C>T)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