Mutation Query
| | | | Allele 1: | S305R | | Allele 2: | P1073L | Allelic information known | | Refine query |
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| | | 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 P1073 | | 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 |
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Mutation Information
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| 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: | Baruffini et al, 2011; | | Description: | Alpers | | Mutations: | P1073L, S305R | | Age group: | infantile | | Age of Onset: 0.75, Age of Patient: n/a, Age of Death: 2 |
| 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 |
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| P1073L | | | | Number of patients: (with P1073L) | 7 | | Found as the only mutation: | 14% of entries (1 patient) | | Found together with: | | | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Kurt et al, 2010; | | Description: | Psychomotor delay, seizures, liver disease, GI dysmotility, lactic acidosis, ptosis, hearing loss. | | Mutations: | A467T, P1073L | | Age group: | infantile | | Age of Onset: 0.01, Age of Patient: n/a, Age of Death: 0.8 |
| Reference: | Kurt et al, 2010; | | Description: | Psychomotor delay, status epilepticus, liver disease, GI dysmotility, lactic acidosis, optic atrophy. | | Mutations: | A467T, P1073L | | Age group: | infantile | | Age of Onset: 0.01, Age of Patient: n/a, Age of Death: 3 |
| Reference: | Kurt et al, 2010; | | Description: | pschomotor delay, seizures, liver disease, GI dysmotility, lactic acidosis. | | Mutations: | G848S, P1073L | | Age group: | infantile | | Age of Onset: 0.4, Age of Patient: n/a, Age of Death: 0.9 |
| Reference: | Tang et al, 2011; | | Description: | Hypotonia, FTT, gastro-oesophaeal reflux. 36% mtDNA copy number in muscle, 62% mtDNA copy number in blood. | | Mutations: | G848S, P1073L | | Age group: | infantile | | Age of Onset: n/a, Age of Patient: 2, Age of Death: n/a |
Back to top | Reference: | Kurt et al, 2010; | | Description: | Psychomotor delay, status epilepticus, liver disease, lactic acidosis, ADHD, mental retardation. | | Mutations: | P1073L, W748S | | Age group: | infantile | | Age of Onset: 0.01, Age of Patient: n/a, Age of Death: 13 |
| Reference: | Baruffini et al, 2011; | | Description: | Alpers | | Mutations: | P1073L, S305R | | Age group: | infantile | | Age of Onset: 0.75, Age of Patient: n/a, Age of Death: 2 |
| Reference: | Rouzier et al, 2013; | | Description: | Myopathy, myoclonic epilepsy, renal tubulopathy, muscle weakness, amyotrophy, myoclonic epilepsy and lipid accumulation. Cerebrospinal fluid and blood lactate concentrations were elevated. Muscle biopsy showed lipid myopathy with no biochemical RC deficiency and neither depletion nor deletions of mtDNA. | | Mutations: | P1073L | | Age group: | childhood | | Age of Onset: 5, Age of Patient: n/a, 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 3 and 3: Age of onset information is extracted from a total of 21 patients and/ or patient families. | Age of onset | | |
21- 11- | 10
| 6
| 2
| 3
| | | infantile | childhd | juvenile | adult | | | 48% | 29% | 10% | 14% | |
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-cluster3 mutations | |
| Symptoms in patients with combination
cluster3:cluster3 | | PEO | 42.9% | | Epilepsy | 33.3% | | Ptosis | 33.3% | | Encephalopathy | 33.3% | | Developmental delay | 33.3% | | Lactic acidosis | 23.8% | | Movement disorder (ataxia) | 19.0% | | Peripheral neuropathy | 19.0% | | Muscle weakness | 19.0% | | Ragged red fibers | 14.3% | | Exercise intolerance | 14.3% | | Dysphagia | 14.3% | | Myoclonic seizures | 9.5% | | Polyneuropathy | 9.5% | | Abnormal muscle histology | 9.5% | | Myopathy | 9.5% | | Liver failure | 9.5% | | Hypotonic | 9.5% | | Dementia | 9.5% | | CPK abnormalities | 9.5% | | +9 other symptoms in under 5.0% of the patients |
| | Data gathered from clinical descriptions for 21 patients |
| Symptoms by group | | CPEO | 52.4% | | Developmental Delay | 42.9% | | Myopathy | 42.9% | | Seizures | 38.1% | | Hepatopathy | 33.3% | | Neuropathy | 28.6% | | Alpers syndrome | 23.8% | | CNS symptoms | 23.8% | | Ataxia | 19.0% | | Hypotonia | 9.5% | | Other | 9.5% | | Unknown | 4.8% |
| | [Show grouping information] |
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