Mutation Query
| | | | Allele 1: | N468D | | Allele 2: | T851A | Allelic information known | | Refine query |
|
| | | 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 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 |
|
|
Mutation Information
|
| 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 |
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 |
|
| 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 |
Back to top |
|
|
|
|
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] |
|
|
|
