Mutation Query
| | | | Allele 1: | R227W | | Allele 2: | D1184N | Allelic information known | | Refine query |
|
| | | Residue R227 | | Cluster assignment: | | | Cluster description: | Distal accessory subunit interface | | Subcluster: | 4A (residues 224-244) | | Subcluster description: | These mutations map to the exo domain along the distal accessory subunit interface. | | POLG domain: | Exonuclease 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 |
|
|
Mutation Information
|
| R227W | | | | Number of patients: (with R227W) | 7 | | Found together with: | |  | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Agostino et al, 2003; | | Description: | PEO, bilateral ptosis, severe limita- tion of ocular motility, and a mosaic distribution of ragged-red and cytochrome c oxidase–negative fibers in the muscle biopsy. All patients had multiple deletions of muscle mtDNA. | | Mutations: | P587L, R227W | | SNPs: | T251I | | Age group: | adult | | Age of Onset: 48, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Giordano et al, 2009; | | Description: | Born with severe hypotonia, general muscle weakness, hearing loss, GI problems, mild cerbral atrophy, mtDNA depletion in muscle and GI, death via respiratory failure at 20 days. | | Mutations: | G848S, R227W | | Age group: | infantile | | Age of Onset: 0.01, Age of Patient: n/a, Age of Death: 0.1 |
| Reference: | Calvo et al, 2012; | | Description: | Complex I deficiency, Hypotonia, lethargy, respiratory distress, metabolic acidosis, FTT, encephalopathy | | Mutations: | G848S, R227W | | Age group: | infantile | | Age of Onset: 0.01, Age of Patient: 0.06, Age of Death: n/a |
Back to top | Reference: | de Vries et al, 2007; | | Description: | Onset at 4 months with FTT, dementia, hypotonia, seizures, myoclonus, GI problems, hepatopathy, hearing loss, delayed myelinisation. Death at 10 months | | Mutations: | A467T, R227W | | Age group: | infantile | | Age of Onset: 0.3, Age of Patient: n/a, Age of Death: 0.8 |
| 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 |
|
| 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: | 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 |
|
|
|
|
|
The following information is based on existing patient data and pathogenic cluster assignment.
Pathogenicity information for a patient with mutations in Clusters 1 and 4: Age of onset information is extracted from a total of 5 patients and/ or patient families. | Age of onset | | |
5- 3- | 4
| 0
| 0
| 1
| | | infantile | childhd | juvenile | adult | | | 80% | 0% | 0% | 20% | |
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 cluster4-cluster1 mutations | |
| Symptoms in patients with combination
cluster1:cluster4 | | Hypotonic | 80.0% | | Failure to thrive | 60.0% | | GI problems | 40.0% | | Hearing loss | 40.0% | | Ragged red fibers | 20.0% | | Muscle weakness | 20.0% | | Ptosis | 20.0% | | PEO | 20.0% | | Encephalopathy | 20.0% | | Retardation | 20.0% | | Respiratory deficiency | 20.0% | | Hepatomegaly | 20.0% | | Microcephaly | 20.0% |
| | Data gathered from clinical descriptions for 5 patients |
| Symptoms by group | | Hypotonia | 80.0% | | Developmental Delay | 60.0% | | Other | 60.0% | | CPEO | 40.0% | | GI symptoms | 40.0% | | Myopathy | 40.0% | | Hepatopathy | 20.0% |
| | [Show grouping information] |
|
|
|
