Mutation Query
| | | | Allele 1: | S1095R | | Allele 2: | D1184N | Allelic information known | | Refine query |
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| | | Residue S1095 | | 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 |
| 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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| S1095R | | | | Number of patients: (with S1095R) | 3 | | Found as the only mutation: | 33% of entries (1 patient) | | Non-allelic with: | A467T (33%) D1184N (33%) |  | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Tang et al, 2011; | | Description: | Hypotonia, hepatic failure, elevated transaminases, respiratory deficiency/failure, FTT, developmental delay, GI reflux, delayed gastric emptying, dicarboxylic aciduria, high CSF protein, abnormal muscle histology, COX deficiency, vomiting. 12% mtDNA copy number in muscle, 42% mtDNA copy number in blood, ETC low. ptosis, poor head control. Central hypotonia, and absent deep tendon reflexes. He developed hypoxia, ascites, tachycardia, intermittent fevers, and sepsis. Some severely cytochrome oxidase-deficient muscle fibers were present. | | Mutations: | A467T, S1095R | | Age group: | infantile | | Age of Onset: 0.333, Age of Patient: n/a, Age of Death: 0.583 |
| 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 |
| Reference: | Wong et al, 2008; | | Description: | Onset 46 years with PEO, muscle weakness, optic atrophy, hearing loss, ptosis. | | Mutations: | S1095R | | Age group: | adult | | Age of Onset: 46, Age of Patient: n/a, 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: | 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 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] |
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