Mutation Query
| | | | Allele 1: | S933R | | Allele 2: | A957V | Allelic information known | | Refine query |
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| | | Residue S933 | | Cluster assignment: | | | Cluster description: | Polymerase active site and environs | | Subcluster: | 1E (residues 914-966) | | Subcluster description: | This subcluster comprises most of the fingers subdomain of the pol domain, including the O-helix and the Pol B motif (Loh and Loeb, 2005). | | POLG domain: | Polymerase domain |
| Residue A957 | | Cluster assignment: | | | Cluster description: | Polymerase active site and environs | | Subcluster: | 1E (residues 914-966) | | Subcluster description: | This subcluster comprises most of the fingers subdomain of the pol domain, including the O-helix and the Pol B motif (Loh and Loeb, 2005). | | POLG domain: | Polymerase domain |
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Mutation Information
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| S933R | | | | Number of patients: (with S933R) | 1 | | Non-allelic with: | A957V (100%) |  | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Tang et al, 2011; | | Description: | Developmental delay, hypotonia, seizures, muscle weakness elevated transaminases, respiratory deficiency, lactic acidosis, high CSF lactate, elevate pyruvate, high CSF protein, abnormal EEG, abnormal MRI, FTT, hypoglycemia. 37% mtDNA copy number in muscle, 41% mtDNA copy number in blood. | | Mutations: | A957V, S933R | | Age group: | infantile | | Age of Onset: n/a, Age of Patient: 0.3, Age of Death: n/a |
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| A957V | | | | Number of patients: (with A957V) | 4 | | Found together with: | | | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Tang et al, 2011; | | Description: | Deceased at 9 months. 30% mtDNA copy number in muscle, 30% mtDNA copy number in blood, 10% mtDNA copy number in liver. | | Mutations: | A957V, G737R | | Age group: | infantile | | Age of Onset: n/a, Age of Patient: 0.4, Age of Death: 0.8 |
| Reference: | Tang et al, 2011; | | Description: | Developmental delay, hypotonia, seizures, muscle weakness elevated transaminases, respiratory deficiency, lactic acidosis, high CSF lactate, elevate pyruvate, high CSF protein, abnormal EEG, abnormal MRI, FTT, hypoglycemia. 37% mtDNA copy number in muscle, 41% mtDNA copy number in blood. | | Mutations: | A957V, S933R | | Age group: | infantile | | Age of Onset: n/a, Age of Patient: 0.3, Age of Death: n/a |
| Reference: | Tang et al, 2011; | | Description: | Developmental delay, hypotonia, dementia/encephalopathy, seizures, myoclonic seizures, elevated transaminases, FTT, abnormal EEG. 81% mtDNA copy number in muscle, 27% mtDNA copy number in blood. | | Mutations: | A957V, C1077G | | Age group: | infantile | | Age of Onset: n/a, Age of Patient: 2, Age of Death: n/a |
| Reference: | Montassir et al, 2014; | | Description: | Myocerebrohepatopathy spectrum (MCHS) disorder. Poor sucking and failure to thrive since, frequent vomiting, developmental regression, developmental delay, emesis, poor weight gain, lethargy. Hypotonia and hepatomegaly. Laboratory tests showed hepatocellular dysfunction and elevated protein and lactate levels in the cerebrospinal fluid. mtDNA depletion. Proximal dominant muscular weakness. All deep tendon reflexes were weak. Myoclonic jerks of the right and left arms were infrequently observed. She died of multiple organ failure caused by hepatic failure at 8 months of age. | | Mutations: | A957V, I1185T | | Age group: | infantile | | Age of Onset: 0.333, Age of Patient: 0.5, Age of Death: 0.666 |
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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 1: Age of onset information is extracted from a total of 20 patients and/ or patient families. | Age of onset | | |
20- 10- | 2
| 7
| 3
| 8
| | | infantile | childhd | juvenile | adult | | | 10% | 35% | 15% | 40% | |
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 cluster1-cluster1 mutations | |
| Symptoms in patients with combination
cluster1:cluster1 | | Developmental delay | 30.0% | | Movement disorder (ataxia) | 25.0% | | PEO | 25.0% | | Muscle weakness | 20.0% | | Hypotonic | 20.0% | | Dementia | 20.0% | | Status epilepticus | 15.0% | | Myopathy | 15.0% | | Ophthalmoplegia | 15.0% | | Liver failure | 15.0% | | Failure to thrive | 15.0% | | Tremor | 15.0% | | Lactic acidosis | 10.0% | | Peripheral neuropathy | 10.0% | | Ptosis | 10.0% | | Encephalopathy | 10.0% | | Vomiting | 10.0% | | Dysphagia | 10.0% | | Hepatomegaly | 10.0% | | Hearing loss | 10.0% | | No known symptoms | 5.0% | | Myoclonic seizures | 5.0% | | Hemiparesis | 5.0% | | Intractable seizure | 5.0% | | Epilepsy | 5.0% | | Cerebellar ataxia | 5.0% | | Polyneuropathy | 5.0% | | Demyelinating neuropathy | 5.0% | | Sensomotor neuropathy | 5.0% | | Exercise intolerance | 5.0% | | Parkinson's disease | 5.0% | | Jaundice | 5.0% | | Headache/ migraine | 5.0% | | Delayed gastric emptying | 5.0% | | Cortical blindness | 5.0% | | Dysarthria | 5.0% | | Respiratory deficiency | 5.0% | | Leigh syndrome | 5.0% | | Areflexia | 5.0% | | CPK abnormalities | 5.0% | | Hypoglycemia | 5.0% |
| | Data gathered from clinical descriptions for 20 patients |
| Symptoms by group | | Developmental Delay | 40.0% | | Myopathy | 35.0% | | Seizures | 35.0% | | CPEO | 30.0% | | Ataxia | 25.0% | | CNS symptoms | 25.0% | | Hepatopathy | 25.0% | | Neuropathy | 25.0% | | Other | 25.0% | | Hypotonia | 20.0% | | GI symptoms | 15.0% | | Alpers syndrome | 5.0% | | Migraines | 5.0% | | Unknown | 5.0% |
| | [Show grouping information] |
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