Mutation Query
| | | | Allele 1: | N468D | | Allele 2: | D1184N | Allelic information known | | Refine query |
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| | | Residue N468 | | Cluster assignment: | | | Cluster description: | Upstream DNA binding channel | | Subcluster: | 2A (residues 463-468) | | Subcluster description: | Subcluster 2A maps to a region of the thumb subdomain of the pol domain at the accessory subunit interface where A467T, N468D and L463F are positioned. | | POLG domain: | Polymerase domain |
| Residue D1184 | | Cluster assignment: | | | Cluster description: | Polymerase active site and environs | | Subcluster: | 1G (residues 1157-1196) | | Subcluster description: | Subcluster 1G (residues 1157-1196) maps to a C-terminal region of the palm subdomain, and forms an anti-parallel beta strand adjacent to the Pol A and Pol C motifs (Loh and Loeb, 2005). | | POLG domain: | Polymerase domain |
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Mutation Information
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| N468D | | | | Number of patients: (with N468D) | 5 | | Found together with: | |  | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Luoma et al, 2004; | | Description: | Ptosis, PEO, Cataracts, sensory axonal neuropathy, moderate motor neuropathy, rigidity, bradykinesia, resting tremor, Parkinsons, muscle weakness. | | Mutations: | A1105T, N468D | | Age group: | adult | | Age of Onset: 30, Age of Patient: 49, Age of Death: 51 |
| Reference: | Luoma et al, 2004; | | Description: | Resting tremor, rigidity, bradykinesia, ptosis, PEO, Excercise intolerance, muscle pain, sensory axonal neuropathy, Parkinsons | | Mutations: | A1105T, N468D | | Age group: | adult | | Age of Onset: 21, Age of Patient: 40, Age of Death: n/a |
| Reference: | Luoma et al, 2004; | | Description: | Resting tremor, rigidity, bradykinesia, ptosis, PEO, general fatigue, muscle weakness, periodic depression, parkinsons, premature menopause. | | Mutations: | A1105T, N468D | | Age group: | adult | | Age of Onset: 32, Age of Patient: 50, Age of Death: n/a |
| Reference: | Gonzalez-Vioque et al, 2006; | | Description: | PEO and tetraparesis, serum CK level elevated. | | Mutations: | D1184N, N468D | | Age group: | adult | | Age of Onset: 32, Age of Patient: n/a, Age of Death: n/a |
Back to top | 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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| D1184N | | | | Number of patients: (with D1184N) | 8 | | Found as the only mutation: | 25% of entries (2 patients) | | Found together with: | | | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Amiot et al, 2009; | | Description: | Peripheral neuropathy, PEO, ataxia, epilepsy, fatty liver | | Mutations: | D1184N, P587L | | SNPs: | T251I | | Age group: | childhood | | Age of Onset: 9, Age of Patient: n/a, Age of Death: 33 |
| Reference: | Amiot et al, 2009; | | Description: | Peripheral neuropathy, PEO, fatty liver | | Mutations: | D1184N, P587L | | SNPs: | T251I | | Age group: | childhood | | Age of Onset: 9, Age of Patient: n/a, Age of Death: 30 |
| Reference: | Rouzier et al, 2013; | | Description: | CPEO, axonal sensory neuronopathy, parkinsonism. late-onset CPEO with a sensory neuropathy and a Parkinsonian syndrome. | | Mutations: | D1184N | | Age group: | adult | | Age of Onset: 70, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Rouzier et al, 2013; | | Description: | CPEO, axonal sensory neuronopathy. | | Mutations: | D1184N | | Age group: | adult | | Age of Onset: 75, Age of Patient: n/a, Age of Death: n/a |
Back to top | Reference: | de Vries et al, 2007; | | Description: | Severe childhood multi-system disorder- age of onset 4-7 months, age of death 26-43 months. Initial symptom was failure to thrive. Other symptoms included severe retardation, GI problems and hypotonia. Also hearing loss and elevated lactate in serum and CSF. Ragged red fibers were observed indicating mtDNA depletion | | Mutations: | D1184N, R227W | | Age group: | infantile | | Age of Onset: 0.5, Age of Patient: n/a, Age of Death: 2 |
| Reference: | Gonzalez-Vioque et al, 2006; | | Description: | PEO and tetraparesis, serum CK level elevated. | | Mutations: | D1184N, N468D | | Age group: | adult | | Age of Onset: 32, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Sarzi et al, 2007; | | Description: | Growth retardation, hypotonia, RC deficiency in muscle, hepatic failure. Onset 5 months of age, death at 11 months of age. 3% mtDNA copy number in muscle, 25 mtDNA copy number in liver. | | Mutations: | D1184N, R807P | | Age group: | infantile | | Age of Onset: 0.5, Age of Patient: n/a, Age of Death: 1 |
| Reference: | Blok et al, 2009; | | Description: | Failure to thrive, feeding problems, intestinal pseudo-obstruction, congenital deafness, demyelinating sensomotor neurpathy, impaired liver function, death at age 3. | | Mutations: | D1184N, S1095R | | Age group: | infantile | | Age of Onset: n/a, Age of Patient: n/a, Age of Death: 3 |
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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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