Mutation Query
| | | | Allele 1: | R627Q | | Allele 2: | G11D, R852C | Allelic information known | | Refine query |
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| | | Residue G11 | | Cluster assignment: | | | Cluster description: | Single Nucleotide Polymorphism | | POLG domain: | N-Terminal domain |
| Residue R627 | | Cluster assignment: | | | Cluster description: | Putative protein-protein interactions | | Subcluster: | 5A (residues 623-648) | | Subcluster description: | Located in the periphery of the IP subdomain of the spacer domain, distant from the DNA binding channel | | POLG domain: | Spacer domain |
| Residue R852 | | 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 |
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Mutation Information
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| R627Q | | | | Number of patients: (with R627Q) | 14 | | Found together with: | |  | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Horvath et al, 2006; | | Description: | Onset at 7 years with encephalopathy, hepatopathy, and SLE seizures. Diagnosed as alpers. Death at 8 years. | | Mutations: | R1096H, R627Q | | Age group: | childhood | | Age of Onset: 7, Age of Patient: n/a, Age of Death: 8 |
| Reference: | Schulte et al, 2009; | | Description: | At 43 years of age, cerebellar ataxia, dysarthria/dysphagia, sensory neuropathy, PEO, distal muscle wasting, mild cerebellar atrophy. | | Mutations: | R1096H, R627Q | | Age group: | adult | | Age of Onset: 25, Age of Patient: 43, Age of Death: n/a |
| Reference: | Schicks et al, 2010; | | Description: | early-onset ataxia, PEO, dysarthria, ptosis, sensory neuropathy, hypoacusis, cerebellar athropy. | | Mutations: | R1096H, R627Q | | Age group: | adult | | Age of Onset: 22, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Tang et al, 2011; | | Description: | Dementia/encephalopathy, infantile spasms, cerebral artery occlusion, headache/migraine, stroke, constipation. 74% mtDNA copy number in blood. | | Mutations: | R627Q, R852C | | SNPs: | G11D | | Age group: | juvenile | | Age of Onset: n/a, Age of Patient: 25, Age of Death: n/a |
Back to top | Reference: | Wong et al, 2008; | | Description: | Ataxia Neuropathy Spectrum, Seizures, PEO, lactic acidosis, stroke, chorea, ataxia, ptosis, retinitis pigmentosa, liver transplans | | Mutations: | R627Q, R852C | | SNPs: | G11D | | Age group: | juvenile | | Age of Onset: 15, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Wong et al, 2008; | | Description: | Seizures, PEO, Ataxia Neuropathy Spectrum, Stroke, chorea, ataxia, ptosis, retinitis pigmentosa, liver transplant | | Mutations: | R627Q, R852C | | SNPs: | G11D | | Age group: | juvenile | | Age of Onset: 15, Age of Patient: 19, Age of Death: n/a |
| Reference: | Luoma et al, 2005; | | Description: | Developed bilateral blepharoptosis in his youth. Neurological examination at the age of 72 showed severe blepharoptosis, lids almost covering his entire pupils. Eye movements were normal, his muscle strength and sensation were good and tendon reflexes were normal, but his gait was unsteady. Early onset ptosis, ataxia | | Mutations: | R627Q | | SNPs: | Q1236H | | Age group: | adult | | Age of Onset: 22, Age of Patient: 73, Age of Death: n/a |
| Reference: | Luoma et al, 2005; | | Description: | developed progressive blepharoptosis at the age of 20 and ophthalmoplegia during subsequent years, at 35, the patient developed progressive unsteadiness of gait. She noted fatigue, myalgia and cramps, which were triggered by moderate exercise. At 44, restless legs syndrome, deficits in memory and concentration, and suffered from recurrent episodes of depression, at 46 showed bilateral blepharoptosis, limited eye movements in all directions except downwards, lateral rotatory nystagmus and slight upbeat nystagmus in upward gaze, but no saccades. She had facial muscle weakness, dysarthria and slight proximal muscle weakness. She had glove and stockinglike hypoesthesia, distally impaired vibration sense, absent ankle reflexes and weak other tendon reflexes, as well as mild dysmetria. Her gait was broad-based, with further impairment with eyes closed. Tandem gait was impaired. deltoid muscle showed myopathic features, structurally abnormal mitochondria with para-crystalline inclusions, | | Mutations: | A467T, R627Q | | SNPs: | Q1236H | | Age group: | adult | | Age of Onset: 20, Age of Patient: 46, Age of Death: n/a |
| Reference: | Luoma et al, 2005; | | Description: | displays mild bilateral blepharoptosis and slight unsteadiness during tandem gait. Early onset ptosis, ataxia | | Mutations: | R627Q | | SNPs: | Q1236H | | Age group: | juvenile | | Age of Onset: n/a, Age of Patient: 19, Age of Death: n/a |
Back to top | Reference: | Deschauer et al, 2007; | | Description: | vomiting, headache, sensory ataxia, areflexia, focal seizures, status epilepticus. MELAS. | | Mutations: | G848S, R627Q | | Age group: | adult | | Age of Onset: 21, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Schulte et al, 2009; | | Description: | At 35 years of age, dysarthria/dysphagia, sensory neuropathy, PEO, distal muscle wasting, phobia anxiety disorder, mild cerebellar atrophy (MRI) | | Mutations: | G848S, R627Q | | Age group: | adult | | Age of Onset: 29, Age of Patient: 35, Age of Death: n/a |
| Reference: | Hanisch et al, 2014; | | Description: | Ataxia, ptosis, myalgia, sensory neuropathy, motor neuropathy, axonal neuropathy, demyelinating neuropathy. | | Mutations: | A467T, R627Q | | Age group: | adult | | Age of Onset: 46, Age of Patient: 50, Age of Death: n/a |
| Reference: | Baruffini et al, 2011; | | Description: | generalized seizures and myoclonic jerks at age 5, ataxia and sensory-axonal peripheral neuropathy onset in teen years. | | Mutations: | R627Q, S305R | | Age group: | childhood | | Age of Onset: 5, Age of Patient: 25, Age of Death: n/a |
| Reference: | Horvath et al, 2006; | | Description: | Onset at 0.5 years with encephalopathy and hepatopathy. Diagnosed as alpers. Death at 1.3 years | | Mutations: | R309H, R627Q | | Age group: | infantile | | Age of Onset: 0.5, Age of Patient: n/a, Age of Death: 1.3 |
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| G11D | | | | Number of patients: (with G11D) | 11 | | Found together with: | | | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Ashley et al, 2008; | | Description: | reported as Alpers, onset at 2 years, presenting encephalopathy with epilepsy, hepatopathy. 22% mtDNA copy number in muscle. | | Mutations: | A467T, R852C | | SNPs: | G11D | | Age group: | infantile | | Age of Onset: 2.25, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Stewart et al, 2009; | | Description: | Alpers, seizures, abnormal liver function, mild lactic acidosis, normal histology of COX fibers. | | Mutations: | A467T, R852C | | SNPs: | G11D | | Age group: | infantile | | Age of Onset: 1.25, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Tang et al, 2011; | | Description: | Dementia/encephalopathy, infantile spasms, cerebral artery occlusion, headache/migraine, stroke, constipation. 74% mtDNA copy number in blood. | | Mutations: | R627Q, R852C | | SNPs: | G11D | | Age group: | juvenile | | Age of Onset: n/a, Age of Patient: 25, Age of Death: n/a |
| Reference: | Tang et al, 2011; | | Description: | Seizures, myoclonic seizures, intractable seizures, hepatic failure, elevated transaminases, Apnes/Hypoventilation, respiratory deficiency/failure, lactic acidosis, organic aciduria/tiglyglycine, low plasma carnitine, abnormal EEG. 108% mtDNA copy number in blood. | | Mutations: | A467T, R852C | | SNPs: | G11D | | Age group: | infantile | | Age of Onset: n/a, Age of Patient: 0.8, Age of Death: n/a |
Back to top | Reference: | Wong et al, 2008; | | Description: | Ataxia Neuropathy Spectrum, Seizures, PEO, lactic acidosis, stroke, chorea, ataxia, ptosis, retinitis pigmentosa, liver transplans | | Mutations: | R627Q, R852C | | SNPs: | G11D | | Age group: | juvenile | | Age of Onset: 15, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Wong et al, 2008; | | Description: | Seizures, PEO, Ataxia Neuropathy Spectrum, Stroke, chorea, ataxia, ptosis, retinitis pigmentosa, liver transplant | | Mutations: | R627Q, R852C | | SNPs: | G11D | | Age group: | juvenile | | Age of Onset: 15, Age of Patient: 19, Age of Death: n/a |
| Reference: | Mehta et al, 2011; | | Description: | progressive cerebellar syndrome, slurred speech, balance disturbances, mild incoordination, type II diabetes mellitus, dysarthria, mild limb dysmetria, mildly impaired tandem gait, cerebellar ataxia. She had polyminimyoclonus of her outstretched hands, a positive glabellar tap and brisk deep tendon reflexes with flexor plantar responses. She had Rigidity in the legs worse than in the arms, brisk reflexes, and mild bilateral bradykinesia in association with dystonic posturing of the left hand. Dystonia. | | Mutations: | R852C | | SNPs: | G11D | | Age group: | adult | | Age of Onset: 49, Age of Patient: 58, Age of Death: n/a |
| Reference: | Ashley et al, 2008; | | Description: | reported as Alpers, onset at 1 years, presenting encephalopathy with epilepsy, hepatopathy, and movement disorder (ataxia). 32% mtDNA copy number in liver. | | Mutations: | R852C, W748S | | SNPs: | G11D | | Age group: | infantile | | Age of Onset: 1, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Stewart et al, 2009; | | Description: | Alpers, Seizures, Epilepsia partialis continua, liver failure, stroke-like episode. | | Mutations: | R852C, W748S | | SNPs: | E1143G, G11D | | Age group: | infantile | | Age of Onset: 1.33, Age of Patient: n/a, Age of Death: n/a |
Back to top | Reference: | Naess et al, 2009; | | Description: | Developmental retardation, Hypotonia, ataxia, seizures myoclonus, abnormal eye movement, gastrointestinal problems, hepatic involvement | | Mutations: | R852C, W748S | | SNPs: | G11D | | Age group: | infantile | | Age of Onset: 0.3, Age of Patient: n/a, Age of Death: 1.1 |
| Reference: | Vasta et al, 2012; | | Description: | PEO, alpers disease, ataxia, seizure, hypotonia, developemental delay, | | Mutations: | R852C, W748S | | SNPs: | E1143G, G11D | | Age group: | infantile | | Age of Onset: 0.001, Age of Patient: n/a, Age of Death: n/a |
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| R852C | | | | Number of patients: (with R852C) | 15 | | Found together with: | | | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Ashley et al, 2008; | | Description: | reported as Alpers, onset at 2 years, presenting encephalopathy with epilepsy, hepatopathy. 22% mtDNA copy number in muscle. | | Mutations: | A467T, R852C | | SNPs: | G11D | | Age group: | infantile | | Age of Onset: 2.25, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Stewart et al, 2009; | | Description: | Alpers, seizures, abnormal liver function, mild lactic acidosis, normal histology of COX fibers. | | Mutations: | A467T, R852C | | SNPs: | G11D | | Age group: | infantile | | Age of Onset: 1.25, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Tang et al, 2011; | | Description: | Seizures, myoclonic seizures, intractable seizures, hepatic failure, elevated transaminases, Apnes/Hypoventilation, respiratory deficiency/failure, lactic acidosis, organic aciduria/tiglyglycine, low plasma carnitine, abnormal EEG. 108% mtDNA copy number in blood. | | Mutations: | A467T, R852C | | SNPs: | G11D | | Age group: | infantile | | Age of Onset: n/a, Age of Patient: 0.8, Age of Death: n/a |
| Reference: | Mehta et al, 2011; | | Description: | progressive cerebellar syndrome, slurred speech, balance disturbances, mild incoordination, type II diabetes mellitus, dysarthria, mild limb dysmetria, mildly impaired tandem gait, cerebellar ataxia. She had polyminimyoclonus of her outstretched hands, a positive glabellar tap and brisk deep tendon reflexes with flexor plantar responses. She had Rigidity in the legs worse than in the arms, brisk reflexes, and mild bilateral bradykinesia in association with dystonic posturing of the left hand. Dystonia. | | Mutations: | R852C | | SNPs: | G11D | | Age group: | adult | | Age of Onset: 49, Age of Patient: 58, Age of Death: n/a |
Back to top | Reference: | Hunter et al, 2011; | | Description: | Myoclonic Seizures, visual disturbance, motor paresis, Focal motor seizures, Epilepsia partialis continua, Developmental Delay or Regression, ataxia, Serum Lactate, liver mtDNA depletion, Alpers | | Mutations: | A467T, R852C | | Age group: | infantile | | Age of Onset: 1.33, Age of Patient: n/a, Age of Death: 5.08 |
| Reference: | McCoy et al, 2011; | | Description: | clonic seizures of the right arm and leg, Coma persisted and was accompanied by hypoglycaemia, tachycardia and oliguria, CSF proteinwas elevated, cortical blindness, anarthria and profound hypotonia, Liver dysfunction, prolonged focal seizures, acute encephalopathy, | | Mutations: | A467T, R852C | | Age group: | infantile | | Age of Onset: 1.75, Age of Patient: n/a, Age of Death: 3.5 |
| Reference: | Ashley et al, 2008; | | Description: | reported as Alpers, onset at 1 years, presenting encephalopathy with epilepsy, hepatopathy, and movement disorder (ataxia). 32% mtDNA copy number in liver. | | Mutations: | R852C, W748S | | SNPs: | G11D | | Age group: | infantile | | Age of Onset: 1, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Stewart et al, 2009; | | Description: | Alpers, Seizures, Epilepsia partialis continua, liver failure, stroke-like episode. | | Mutations: | R852C, W748S | | SNPs: | E1143G, G11D | | Age group: | infantile | | Age of Onset: 1.33, Age of Patient: n/a, Age of Death: n/a |
Back to top | Reference: | Naess et al, 2009; | | Description: | Developmental retardation, Hypotonia, ataxia, seizures myoclonus, abnormal eye movement, gastrointestinal problems, hepatic involvement | | Mutations: | R852C, W748S | | SNPs: | G11D | | Age group: | infantile | | Age of Onset: 0.3, Age of Patient: n/a, Age of Death: 1.1 |
| Reference: | Vasta et al, 2012; | | Description: | PEO, alpers disease, ataxia, seizure, hypotonia, developemental delay, | | Mutations: | R852C, W748S | | SNPs: | E1143G, G11D | | Age group: | infantile | | Age of Onset: 0.001, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Sofou et al, 2013; | | Description: | Alpers/ Alpers–Huttenlocher. | | Mutations: | Q497H, R852C, W748S | | SNPs: | E1143G | | Age group: | infantile | | Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Tang et al, 2011; | | Description: | Dementia/encephalopathy, infantile spasms, cerebral artery occlusion, headache/migraine, stroke, constipation. 74% mtDNA copy number in blood. | | Mutations: | R627Q, R852C | | SNPs: | G11D | | Age group: | juvenile | | Age of Onset: n/a, Age of Patient: 25, Age of Death: n/a |
| Reference: | Wong et al, 2008; | | Description: | Ataxia Neuropathy Spectrum, Seizures, PEO, lactic acidosis, stroke, chorea, ataxia, ptosis, retinitis pigmentosa, liver transplans | | Mutations: | R627Q, R852C | | SNPs: | G11D | | Age group: | juvenile | | Age of Onset: 15, Age of Patient: n/a, Age of Death: n/a |
Back to top | Reference: | Wong et al, 2008; | | Description: | Seizures, PEO, Ataxia Neuropathy Spectrum, Stroke, chorea, ataxia, ptosis, retinitis pigmentosa, liver transplant | | Mutations: | R627Q, R852C | | SNPs: | G11D | | Age group: | juvenile | | Age of Onset: 15, Age of Patient: 19, Age of Death: n/a |
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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 5: Age of onset information is extracted from a total of 51 patients and/ or patient families. | Age of onset | | |
51- 26- | 24
| 13
| 6
| 8
| | | infantile | childhd | juvenile | adult | | | 47% | 25% | 12% | 16% | |
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 cluster5-cluster1 mutations | |
| Symptoms in patients with combination
cluster1:cluster5 | | Movement disorder (ataxia) | 41.2% | | Developmental delay | 37.3% | | Encephalopathy | 33.3% | | Epilepsy | 31.4% | | Liver failure | 23.5% | | Myoclonic seizures | 19.6% | | Epilepsia partialis | 19.6% | | Ptosis | 15.7% | | PEO | 15.7% | | Lactic acidosis | 13.7% | | Status epilepticus | 13.7% | | Hypotonic | 13.7% | | Headache/ migraine | 11.8% | | Dysarthria | 11.8% | | Peripheral neuropathy | 9.8% | | Intractable seizure | 7.8% | | Stroke | 7.8% | | Hepatocerebral | 7.8% | | Muscle weakness | 5.9% | | Exercise intolerance | 5.9% | | Vomiting | 5.9% | | +37 other symptoms in under 5.0% of the patients |
| | Data gathered from clinical descriptions for 51 patients |
| Symptoms by group | | Seizures | 64.7% | | Developmental Delay | 47.1% | | Ataxia | 43.1% | | Hepatopathy | 37.3% | | Alpers syndrome | 31.4% | | CNS symptoms | 27.5% | | CPEO | 25.5% | | Neuropathy | 17.6% | | Other | 15.7% | | Hypotonia | 13.7% | | Migraines | 11.8% | | Myopathy | 11.8% | | GI symptoms | 9.8% | | Unknown | 3.9% |
| | [Show grouping information] |
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