Mutation Query
| | | | Allele 1: | S305R | | Allele 2: | R627Q | Allelic information known | | Refine query |
|
| | | Residue S305 | | 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 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 |
|
|
Mutation Information
|
| S305R | | | | Number of patients: (with S305R) | 6 | | Found as the only mutation: | 17% of entries (1 patient) | | Found together with: | |  | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Blok et al, 2009; | | Description: | Alpers, died at age four. Sister also died at age 4 . | | Mutations: | A467T, S305R | | Age group: | childhood | | Age of Onset: n/a, Age of Patient: n/a, Age of Death: 4 |
| Reference: | Tang et al, 2011; | | Description: | Liver failure. 51% mtDNA copy number in muscle, 9% mtDNA copy number in liver, 87% mtDNA copy number in blood. | | Mutations: | A467T, S305R | | Age group: | infantile | | Age of Onset: n/a, Age of Patient: 1, Age of Death: n/a |
| Reference: | Hunter et al, 2011; | | Description: | Myoclonic Seizures, Focal motor seizures, Developmental Delay or Regression, visual disturbance, Multi-organ failure, pancreatitis Abnormal Liver Enzymes, Serum Lactate, liver mtDNA depletion, Alpers | | Mutations: | A467T, S305R | | Age group: | childhood | | Age of Onset: 3, Age of Patient: n/a, Age of Death: 3.67 |
| 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 |
Back to top | Reference: | Wong et al, 2008; | | Description: | developmental delay, dementia, lactic acidosis, alpers | | Mutations: | S305R | | Age group: | infantile | | Age of Onset: 1, Age of Patient: n/a, Age of Death: n/a |
|
| 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 |
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 3 and 5: Age of onset information is extracted from a total of 15 patients and/ or patient families. | Age of onset | | |
15- 8- | 3
| 3
| 0
| 9
| | | infantile | childhd | juvenile | adult | | | 20% | 20% | 0% | 60% | |
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-cluster5 mutations | |
| Symptoms in patients with combination
cluster3:cluster5 | | PEO | 53.3% | | Ptosis | 40.0% | | Epilepsy | 26.7% | | Movement disorder (ataxia) | 26.7% | | Dysarthria | 26.7% | | Encephalopathy | 20.0% | | Dysphagia | 20.0% | | Lactic acidosis | 13.3% | | Status epilepticus | 13.3% | | Peripheral neuropathy | 13.3% | | Muscle weakness | 13.3% | | Myopathy | 13.3% | | Diplopia | 13.3% | | Developmental delay | 13.3% | | No known symptoms | 6.7% | | Myoclonic seizures | 6.7% | | Hemiparesis | 6.7% | | Focal seizures | 6.7% | | Epilepsia partialis | 6.7% | | Cerebellar ataxia | 6.7% | | Cerebellar atrophy | 6.7% | | Sensory ataxia | 6.7% | | Ragged red fibers | 6.7% | | Mitochondrial myopathy | 6.7% | | Ophthalmoplegia | 6.7% | | Stroke | 6.7% | | Parkinson's disease | 6.7% | | Liver failure | 6.7% | | Liver dysfunction | 6.7% | | Headache/ migraine | 6.7% | | Psychomotor delay | 6.7% | | Retardation | 6.7% | | Pschomotor regression | 6.7% | | Lowered consciousness | 6.7% | | Vomiting | 6.7% | | Cortical blindness | 6.7% | | Distal muscle wasting | 6.7% | | Stroke-like episodes | 6.7% | | Tremor | 6.7% |
| | Data gathered from clinical descriptions for 15 patients |
| Symptoms by group | | CPEO | 60.0% | | Seizures | 40.0% | | CNS symptoms | 33.3% | | Developmental Delay | 33.3% | | Ataxia | 26.7% | | Myopathy | 26.7% | | Hepatopathy | 20.0% | | Alpers syndrome | 13.3% | | Neuropathy | 13.3% | | Other | 13.3% | | GI symptoms | 6.7% | | Migraines | 6.7% | | Unknown | 6.7% |
| | [Show grouping information] |
|
|
|
