Mutation Query
| | | | Allele 1: | T851A | | Allele 2: | R1047W | Allelic information known | | Refine query |
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| | | Residue T851 | | Cluster assignment: | | | Cluster description: | Polymerase active site and environs | | Subcluster: | 1D (residues 848-895) | | Subcluster description: | This subcluster forms a large portion of the pol active site and contains two highly conserved motifs that are found in all family A polymerases: the RR loop (motif 2) and motif A (Loh and Loeb, 2005). | | POLG domain: | Polymerase domain |
| Residue R1047 | | Cluster assignment: | | | Cluster description: | Partitioning loop | | Subcluster: | 3D (residues 1047-1096) | | Subcluster description: | The partitioning loop, which is a novel structural module conserved in PolG (residues 1050-1095) that is located between the fingers and palm subdomains of the pol domain, and is not present in any other known DNA polymerase (Euro et al, 2011). | | POLG domain: | Polymerase domain |
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Mutation Information
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| T851A | | | | Number of patients: (with T851A) | 4 | | Found together with: | |  | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Wiltshire et al, 2008; | | Description: | Juvenile Alpers, migraines at 12 years, ataxia, peripheral neuropathy, seizures, VPA-induced hepatopathy. | | Mutations: | R1047W, T851A | | Age group: | childhood | | Age of Onset: 12, Age of Patient: n/a, Age of Death: 17 |
| Reference: | Ashley et al, 2008; | | Description: | Onset at 6 months of age, epilepsy, hepatopathy. 4% mtDNA copy number in liver, 32% mtDNA copy number in muscle. | | Mutations: | H277L, T851A | | Age group: | infantile | | Age of Onset: 0.5, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Woodbridge et al, 2012; | | Description: | CPEO, Seizures, neuropathy, ataxia, dysphagia/ dysarthria, bowel pseudo-obstruction, | | Mutations: | T851A | | SNPs: | P163S | | Age group: | adult | | Age of Onset: 21, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Woodbridge et al, 2012; | | Description: | CPEO, neuropathy, ataxia, hepatopathy, dysphagia/ dysarthria, gastrointestinal symptoms, severe diarrhoea alternating with constipation, | | Mutations: | N468D, T851A | | Age group: | childhood | | Age of Onset: n/a, Age of Patient: 49, Age of Death: n/a |
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| R1047W | | | | Number of patients: (with R1047W) | 3 | | Non-allelic with: | A862T (67%) T851A (33%) | | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Stewart et al, 2009; | | Description: | PEO with ataxia, SCA-like phenotype in siblings, multiple deletions in muscle mtDNA detected via LPCR. 3% COX deficient fibers. | | Mutations: | A862T, R1047W | | Age group: | adult | | Age of Onset: 61, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Lax et al, 2012a; | | Description: | CPEO, Ptosis, Peripheral neuropathy, COX-deficient fibers, presence of mitochondrial dna deletions in muscle, ataxia, dysarthria, Axonal sensory neuropathy /neuronopathy, Distal and proximal neurogenic change. | | Mutations: | A862T, R1047W | | Age group: | adult | | Age of Onset: 22, Age of Patient: 61, Age of Death: n/a |
| Reference: | Wiltshire et al, 2008; | | Description: | Juvenile Alpers, migraines at 12 years, ataxia, peripheral neuropathy, seizures, VPA-induced hepatopathy. | | Mutations: | R1047W, T851A | | Age group: | childhood | | Age of Onset: 12, Age of Patient: n/a, Age of Death: 17 |
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The following information is based on existing patient data and pathogenic cluster assignment.
Pathogenicity information for a patient with mutations in Clusters 1 and 3: Age of onset information is extracted from a total of 18 patients and/ or patient families. | Age of onset | | |
18- 9- | 9
| 2
| 2
| 5
| | | infantile | childhd | juvenile | adult | | | 50% | 11% | 11% | 28% | |
All mutations mapping within the pathogenic clusters are at high risk for pathogenicity. In general, a patient must have a pathogenic mutation in both of his/ her POLG genes to develop a POLG-related syndrome. | Symptoms described in patients with cluster1-cluster3 mutations | |
| Symptoms in patients with combination
cluster1:cluster3 | | Movement disorder (ataxia) | 44.4% | | Encephalopathy | 33.3% | | Developmental delay | 33.3% | | Epilepsy | 27.8% | | PEO | 27.8% | | Failure to thrive | 22.2% | | Hypotonic | 22.2% | | Peripheral neuropathy | 16.7% | | Ptosis | 16.7% | | Dysarthria | 16.7% | | Lactic acidosis | 11.1% | | Ragged red fibers | 11.1% | | Muscle weakness | 11.1% | | Liver failure | 11.1% | | Headache/ migraine | 11.1% | | Dementia | 11.1% | | Retardation | 11.1% | | GI dysmotility | 11.1% | | Myoclonic seizures | 5.6% | | Sensory ataxia | 5.6% | | Polyneuropathy | 5.6% | | Demyelinating neuropathy | 5.6% | | Axonal sensorimotor polyneuropathy | 5.6% | | Abnormal muscle ultrastructure | 5.6% | | Exercise intolerance | 5.6% | | Cox-negative | 5.6% | | Diplopia | 5.6% | | Liver dysfunction | 5.6% | | Growth retardation | 5.6% | | Vomiting | 5.6% | | GI reflux | 5.6% | | Cyclic vomiting | 5.6% | | Delayed gastric emptying | 5.6% | | Tremor | 5.6% | | Hearing loss | 5.6% |
| | Data gathered from clinical descriptions for 18 patients |
| Symptoms by group | | Developmental Delay | 50.0% | | Ataxia | 44.4% | | CPEO | 38.9% | | Seizures | 33.3% | | Neuropathy | 27.8% | | Alpers syndrome | 22.2% | | CNS symptoms | 22.2% | | Hypotonia | 22.2% | | GI symptoms | 16.7% | | Hepatopathy | 16.7% | | Myopathy | 16.7% | | Migraines | 11.1% | | Other | 5.6% |
| | [Show grouping information] |
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