Mutation Query
| | | | Allele 1: | R597W | | Allele 2: | R597W | Allelic information known | | Refine query |
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| | | 597 |  |  |
| | Residue R597 | | Cluster assignment: | | | Cluster description: | Upstream DNA binding channel | | Subcluster: | 2C (residues 561-617) | | Subcluster description: | Subcluster 2C contains motif 1, which in Pol I was shown to fold into a loop that binds DNA in the channel (Loh and Loeb, 2005). Motif 1, together with subcluster 2D, form the major face of the putative DNA binding channel. | | POLG domain: | Spacer domain |
| Residue R597 | | Cluster assignment: | | | Cluster description: | Upstream DNA binding channel | | Subcluster: | 2C (residues 561-617) | | Subcluster description: | Subcluster 2C contains motif 1, which in Pol I was shown to fold into a loop that binds DNA in the channel (Loh and Loeb, 2005). Motif 1, together with subcluster 2D, form the major face of the putative DNA binding channel. | | POLG domain: | Spacer domain |
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Mutation Information
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| R597W | | | | Number of patients: (with R597W) | 4 | | Non-allelic with: | R597W (75%) A467T (25%) |  | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Stewart et al, 2009; | | Description: | Onset 10 years of age presenting as PEO with ataxia, myopathy, exercise intolerance, peripheral neuropathy, dysarthria, GI problems multiple deletions in muscle mtDNA. 1%RRF, 18% COX deficient fibers. | | Mutations: | R597W, R597W | | Age group: | childhood | | Age of Onset: 10, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Tang et al, 2011; | | Description: | Seizures and developing PEO, peripheral neuropathy, and death occurred after VPA treatment. 53% mtDNA copy number in muscle. | | Mutations: | R597W, R597W | | Age group: | juvenile | | Age of Onset: n/a, Age of Patient: 18, Age of Death: n/a |
| Reference: | Saneto et al, 2010; | | Description: | Complex partial seizures at age 14, treated with VPA. In 2 months, he had bilateral foot drop, pes cavus, and mild ophthalmoplegia without obvious cognitive abnormality and peripheral neuropathy, pancreatitis that progressed to multiple organ failure including kidneys, liver, lung, and pancreas. VPA was stopped, ragged red fibers, and COX-negative fibers, Although VPA was stopped, his liver function impairment progressed. Despite aggressive supportive care, he unfortunately died of sepsis and adult respiratory distress syndrome 27 days after the biopsy | | Mutations: | R597W, R597W | | Age group: | juvenile | | Age of Onset: 14, Age of Patient: 18, Age of Death: 18.5 |
| Reference: | Tang et al, 2011; | | Description: | Dementia/encephalopathy, ataxia, peripheral neuropathy, ptosis, abnormal muscle histology, abnormal muscle ultrastructure, abnormal respiratory enzyms, large mitochondrial/ proliferation, COX deficiency, ragged red fibers. 100% mtDNA copy number in blood. | | Mutations: | A467T, R597W | | Age group: | adult | | Age of Onset: n/a, Age of Patient: 26, Age of Death: n/a |
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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 2 and 2: Age of onset information is extracted from a total of 69 patients and/ or patient families. | Age of onset | | |
69- 35- | 7
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| 24
| | | infantile | childhd | juvenile | adult | | | 10% | 25% | 30% | 35% | |
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 cluster2-cluster2 mutations | |
| Symptoms in patients with combination
cluster2:cluster2 | | Movement disorder (ataxia) | 53.6% | | PEO | 36.2% | | Ptosis | 27.5% | | Epilepsy | 26.1% | | Peripheral neuropathy | 26.1% | | Myoclonic seizures | 24.6% | | Status epilepticus | 18.8% | | Encephalopathy | 18.8% | | Ophthalmoplegia | 17.4% | | Dysarthria | 15.9% | | Nystagmus | 14.5% | | Ragged red fibers | 13.0% | | Myopathy | 13.0% | | Stroke | 13.0% | | Headache/ migraine | 13.0% | | Developmental delay | 13.0% | | Epilepsia partialis | 11.6% | | Demyelinating neuropathy | 11.6% | | Sensory ataxia | 10.1% | | Muscle weakness | 10.1% | | Liver failure | 8.7% | | Tremor | 8.7% | | Cox-negative | 7.2% | | Dysphagia | 7.2% | | +34 other symptoms in under 5.0% of the patients |
| | Data gathered from clinical descriptions for 69 patients |
| Symptoms by group | | CPEO | 58.0% | | Ataxia | 55.1% | | Seizures | 53.6% | | CNS symptoms | 43.5% | | Neuropathy | 40.6% | | Myopathy | 31.9% | | Developmental Delay | 23.2% | | Hepatopathy | 15.9% | | GI symptoms | 13.0% | | Migraines | 13.0% | | Other | 13.0% | | Alpers syndrome | 10.1% | | Hypotonia | 4.3% | | Unknown | 1.4% |
| | [Show grouping information] |
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