Mutation Query
| | | | Allele 1: | K319E | | Allele 2: | R869Q | Allelic information known | | Refine query |
|
| | | Residue K319 | | Cluster assignment: | | | Cluster description: | Partitioning loop | | Subcluster: | 3B (residues 303-319) | | Subcluster description: | A helix-coil-helix module (residues 295-312) located in the Exo domain that has been termed the "orienter" module | | POLG domain: | Exonuclease domain |
| Residue R869 | | 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
|
| K319E | | | | Number of patients: (with K319E) | 1 | | Non-allelic with: | R869Q (100%) |  | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Tang et al, 2011; | | Description: | Headaches/migraines, ataxia, peripheral neuropathy, muscle weakness, CPEO, abnromal EMG/NCV, ptosis, CPF abnormalities, abnormal histology, abnormal muscle ultrastructure, COX deficiency, ragged red fibers. 114% mtDNA copy number in blood. | | Mutations: | K319E, R869Q | | Age group: | adult | | Age of Onset: n/a, Age of Patient: 44, Age of Death: n/a |
|
| R869Q | | | | Number of patients: (with R869Q) | 2 | | Found together with: | | | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Tang et al, 2011; | | Description: | Headaches/migraines, ataxia, peripheral neuropathy, muscle weakness, CPEO, abnromal EMG/NCV, ptosis, CPF abnormalities, abnormal histology, abnormal muscle ultrastructure, COX deficiency, ragged red fibers. 114% mtDNA copy number in blood. | | Mutations: | K319E, R869Q | | Age group: | adult | | Age of Onset: n/a, Age of Patient: 44, Age of Death: n/a |
| Reference: | Hanisch et al, 2014; | | Description: | Pareses, ptosis, ataxia, sensory neoropathy, motor neuropathy, axonal neuropathy, demyelinating neuropathy. | | Mutations: | P587L, R869Q | | SNPs: | T251I | | Age group: | adult | | Age of Onset: 29, Age of Patient: 34, Age of Death: n/a |
|
|
|
|
|
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 cluster3-cluster1 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] |
|
|
|
