Mutation Query
| | | | Allele 1: | H932Y | | Allele 2: | G1051R | Allelic information known | | Refine query |
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| | | Residue H932 | | Cluster assignment: | | | Cluster description: | Polymerase active site and environs | | Subcluster: | 1E (residues 914-966) | | Subcluster description: | This subcluster comprises most of the fingers subdomain of the pol domain, including the O-helix and the Pol B motif (Loh and Loeb, 2005). | | POLG domain: | Polymerase domain |
| Residue G1051 | | 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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| H932Y | | | | Number of patients: (with H932Y) | 4 | | Found together with: | |  | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Tang et al, 2011; | | Description: | Peripheral neuropathy, exercise intolerance, muscle cramps after exercise, easy fatigability, arrythmia, CPEO, abnormal EMG/NCV, ptosis, cataract, abnormal muscle histology, abnormal muscle ultrastructure, COX deficiency, ragged red fibers. 123% mtDNA copy number in blood. | | Mutations: | H932Y, P587L | | SNPs: | T251I | | Age group: | adult | | Age of Onset: n/a, Age of Patient: 31, Age of Death: n/a |
| Reference: | Tang et al, 2011; | | Description: | Peripheral neuropathy, ptosis, muscle weakness, CPK abnormalities. 77% mtDNA copy number in blood. | | Mutations: | H932Y, P587L | | SNPs: | T251I | | Age group: | adult | | Age of Onset: n/a, Age of Patient: 41, Age of Death: n/a |
| Reference: | Mancuso et al, 2004a; | | Description: | PEO, erectile dysfunction, progressive hearing loss, dysarthria, ataxic gait, Romberg sign, severe peripheral axonal sensorimotor polyneuropathy. | | Mutations: | G1051R, H932Y | | Age group: | juvenile | | Age of Onset: 18, Age of Patient: 35, Age of Death: n/a |
| Reference: | Giordano et al, 2010; | | Description: | Isolated distal myopathy of the upper extremities, cytochrome c oxidase deficient fibers, muscle weakness. mtDNA depletion. Reduced Deep tendon reflexes in the upper extremities. | | Mutations: | H932Y | | SNPs: | R386C | | Age group: | adult | | Age of Onset: 24, Age of Patient: 27, Age of Death: n/a |
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| G1051R | | | | Number of patients: (with G1051R) | 1 | | Non-allelic with: | H932Y (100%) | | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Mancuso et al, 2004a; | | Description: | PEO, erectile dysfunction, progressive hearing loss, dysarthria, ataxic gait, Romberg sign, severe peripheral axonal sensorimotor polyneuropathy. | | Mutations: | G1051R, H932Y | | Age group: | juvenile | | Age of Onset: 18, Age of Patient: 35, 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 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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