Mutation Query
| | | | Allele 1: | R579W | | Allele 2: | A889T | Allelic information known | | Refine query |
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| | | Residue R579 | | 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 A889 | | 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 |
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Mutation Information
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| R579W | | | | Number of patients: (with R579W) | 1 | | Non-allelic with: | A889T (100%) |  | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Filosto et al, 2003; | | Description: | Onset at age 30 with ptosis, later development of ataxia orthostatic dizziness, cataracts, GI dysmotility with diarrhea and constipation. | | Mutations: | A889T, R579W | | Age group: | adult | | Age of Onset: 30, Age of Patient: n/a, Age of Death: n/a |
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| A889T | | | | Number of patients: (with A889T) | 3 | | Allelic with: | E1143G (67%) | | Non-allelic with: | R579W (33%) | | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Hisama et al, 2005; | | Description: | Presented with ataxia and transient diplopia at age 25 and showed ptosis, external ophthalmoplegia, nystagmus, had a mild tremor of outstretched hands, marked dysmetria, Romberg sign, severe ataxia, was unable to stand on one foot, multiple mtDNA deletions in muscle. | | Mutations: | A889T | | SNPs: | E1143G | | Age group: | adult | | Age of Onset: n/a, Age of Patient: 25, Age of Death: n/a |
| Reference: | Hisama et al, 2005; | | Description: | presented at age 7 years with gait difficulty and pes cavus. He developed upper extremity tremor, scanning speech, and horizontal nystagmus by age 15. at age 20 showed ptosis, external ophthalmoplegia, mildly decreased vibration and pin prick sensation, intention tremor, absent ankle and brachioradialis reflexes, and ataxic gait. Over the next 5 years, he experienced progression of the ptosis and ophthalmoplegia. The tremor became disabling at rest and with action, and he became wheelchair-dependent. | | Mutations: | A889T | | SNPs: | E1143G | | Age group: | childhood | | Age of Onset: 7, Age of Patient: 20, Age of Death: n/a |
| Reference: | Filosto et al, 2003; | | Description: | Onset at age 30 with ptosis, later development of ataxia orthostatic dizziness, cataracts, GI dysmotility with diarrhea and constipation. | | Mutations: | A889T, R579W | | Age group: | adult | | Age of Onset: 30, Age of Patient: n/a, 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 1 and 2: Age of onset information is extracted from a total of 93 patients and/ or patient families. | Age of onset | | |
93- 47- | 57
| 13
| 2
| 21
| | | infantile | childhd | juvenile | adult | | | 61% | 14% | 2% | 23% | |
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-cluster1 mutations | |
| Symptoms in patients with combination
cluster1:cluster2 | | Encephalopathy | 43.8% | | Developmental delay | 43.8% | | Epilepsy | 35.4% | | Movement disorder (ataxia) | 19.8% | | PEO | 19.8% | | Dementia | 18.8% | | Ptosis | 17.7% | | Hypotonic | 16.7% | | Lactic acidosis | 14.6% | | Liver failure | 12.5% | | Myoclonic seizures | 10.4% | | Epilepsia partialis | 10.4% | | Peripheral neuropathy | 9.4% | | Failure to thrive | 9.4% | | Ragged red fibers | 8.3% | | Muscle weakness | 8.3% | | Liver dysfunction | 8.3% | | Status epilepticus | 7.3% | | Intractable seizure | 7.3% | | Myopathy | 7.3% | | Hypoglycemia | 7.3% | | Tremor | 6.3% | | Stroke | 5.2% | | +44 other symptoms in under 5.0% of the patients |
| | Data gathered from clinical descriptions for 96 patients |
| Symptoms by group | | Developmental Delay | 58.3% | | Seizures | 58.3% | | Alpers syndrome | 33.3% | | Hepatopathy | 30.2% | | CPEO | 27.1% | | Other | 22.9% | | Myopathy | 20.8% | | Ataxia | 19.8% | | Hypotonia | 16.7% | | Neuropathy | 15.6% | | CNS symptoms | 14.6% | | GI symptoms | 8.3% | | Migraines | 3.1% | | Unknown | 3.1% |
| | [Show grouping information] |
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