Mutation Query
| | | | Allele 1: | L304R | | Allele 2: | G737R | Allelic information known | | Refine query |
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| | | Residue L304 | | 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 G737 | | Cluster assignment: | | | Cluster description: | Putative protein-protein interactions | | Subcluster: | 5B (residues 737-749) | | Subcluster description: | Located in the periphery of the IP subdomain of the spacer domain, distant from the DNA binding channel | | POLG domain: | Spacer domain |
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Mutation Information
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| L304R | | | | Number of patients: (with L304R) | 23 | | Found as the only mutation: | 13% of entries (3 patients) | | Found together with: | |  | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Ashley et al, 2008; | | Description: | Relatively Mild phenotype | | Mutations: | L304R, L304R | | Age group: | childhood | | Age of Onset: 10, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Tang et al, 2011; | | Description: | CPEO, muscle weakness, ptosis, ataxia. 53% mtDNA copy number in blood. | | Mutations: | L304R, L304R | | Age group: | childhood | | Age of Onset: n/a, Age of Patient: 10, Age of Death: n/a |
| Reference: | Tang et al, 2011; | | Description: | CPEO, ptosis, ataxia, abnormal EMG/NCV, cerebellar atrophy, large mitochondrial proliferation, ragged red fibers, easy fatigability, abnormal muscle histology, hypotonia, lactic acidosis, high CSF lactate, organic aciduria/tiglyglycine, low plasma carnitine. 36% mtDNA copy number in muscle, 22% mtDNA copy number in blood. | | Mutations: | L304R, L304R | | Age group: | childhood | | Age of Onset: n/a, Age of Patient: 9, Age of Death: n/a |
| Reference: | Tang et al, 2011; | | Description: | Peripheral neuropathy exercise intolerance, easy fatigability, CPEO, abnormal EMG/NCV, ptosis, lactic acidosis, CPK abnormalities, short stature, FTT, abnormal VERS, developmental delay, abnormal respiratory enzymes, ragged red fibers. 37% mtDNA copy number in muscle, 20% mtDNA copy number in blood. | | Mutations: | L304R, L304R | | Age group: | childhood | | Age of Onset: n/a, Age of Patient: 12, Age of Death: n/a |
Back to top | Reference: | Tang et al, 2011; | | Description: | Peripheral neuropathy exercise intolerance, muscle weakness, easy fatigability, abnormal EMG/NCV, ptosis, CPK abnormalities, short stature, abnormal muscle histology, ragged red fibers, elevated pyruvate. 45% mtDNA copy number in blood. | | Mutations: | L304R, L304R | | Age group: | juvenile | | Age of Onset: n/a, Age of Patient: 23, Age of Death: n/a |
| Reference: | Tang et al, 2011; | | Description: | Peripheral neuropathy, exercise intolerance, muscle weakness, abnormal EMG/NCV, ptosis, lactic acidosis, COX deficiency, CPEO. 58% mtDNA copy number in blood. | | Mutations: | L304R, L304R | | Age group: | childhood | | Age of Onset: n/a, Age of Patient: 9, Age of Death: n/a |
| Reference: | Tang et al, 2011; | | Description: | Seizures, ptosis, elevated transaminases, lactic acidosis, elevated dopamine, abnormal MRI. 48% mtDNA copy number in muscle, 26% mtDNA copy number in liver. | | Mutations: | L304R, L304R | | Age group: | infantile | | Age of Onset: n/a, Age of Patient: 4, Age of Death: n/a |
| Reference: | Van Goethem et al, 2003a; | | Description: | sensory ataxic neuropathy, PEO, dysarthria. | | Mutations: | A467T, L304R | | Age group: | adult | | Age of Onset: 25, Age of Patient: n/a, Age of Death: n/a |
Back to top | Reference: | Van Goethem et al, 2001; | | Description: | ocular symptoms, psychiatric symptoms, ptosis, opthalmoplegia, muscle weakness, distal sensory neuropathy, areflexia, pes cavus. | | Mutations: | A467T, L304R | | Age group: | adult | | Age of Onset: 25, Age of Patient: 38, Age of Death: n/a |
| Reference: | Van Goethem et al, 2001; | | Description: | ocular symptoms, ptosis, opthalmoplegia, dysphagia, muscle weakness, areflexia, retinopathy. | | Mutations: | A467T, L304R | | Age group: | adult | | Age of Onset: 24, Age of Patient: 34, Age of Death: n/a |
| Reference: | Van Goethem et al, 2001; | | Description: | psychiatric symptoms, ptosis, opthalmoplegia, dysphonia, dysphagia, muscle weakness, loss of weight, areflexia. | | Mutations: | A467T, L304R | | Age group: | juvenile | | Age of Onset: 16, Age of Patient: 28, Age of Death: n/a |
| Reference: | Bindu et al, 2016; | | Description: | CPEO, Sensory motor axonal neuropathy | | Mutations: | L304R | | Age group: | adult | | Age of Onset: n/a, Age of Patient: 26, Age of Death: n/a |
| Reference: | Bindu et al, 2016; | | Description: | Mitochondrial spinocerebellar ataxia epilepsy syndrome, motor axonal neuropathy | | Mutations: | L304R | | Age group: | childhood | | Age of Onset: n/a, Age of Patient: 6, Age of Death: n/a |
Back to top | Reference: | Bindu et al, 2016; | | Description: | SANDO syndrome, Sensory motor demyelinating neuropathy | | Mutations: | L304R | | Age group: | childhood | | Age of Onset: n/a, Age of Patient: 10, Age of Death: n/a |
| Reference: | Horvath et al, 2006; | | Description: | PEO, Neuropathy. Affect sibling. | | Mutations: | L304R, P587L | | SNPs: | T251I | | Age group: | adult | | Age of Onset: 60, Age of Patient: 68, Age of Death: n/a |
| Reference: | Horvath et al, 2006; | | Description: | PEO, myopathy, ataxia. | | Mutations: | L304R, P587L | | SNPs: | T251I | | Age group: | adult | | Age of Onset: 45, Age of Patient: 74, Age of Death: n/a |
| Reference: | Tang et al, 2011; | | Description: | Cerebral cavernous malformation, teen onset CPEO. 110% mtDNA copy number in blood. | | Mutations: | A143V, L304R | | Age group: | juvenile | | Age of Onset: n/a, Age of Patient: 22, Age of Death: n/a |
| Reference: | Tang et al, 2011; | | Description: | Muscle weakness, ptosis, ophthalmoparesis/CPEO. 61% mtDNA copy number in blood. | | Mutations: | G737R, L304R | | Age group: | adult | | Age of Onset: n/a, Age of Patient: 54, Age of Death: n/a |
Back to top | Reference: | Naimi et al, 2006; | | Description: | SCAE, age of onset 20, death at 27, ptosis and multiple deletions in muscle. | | Mutations: | L304R, W748S | | SNPs: | E1143G | | Age group: | adult | | Age of Onset: 20, Age of Patient: n/a, Age of Death: 27 |
| Reference: | Tang et al, 2011; | | Description: | Age 10, encephalopathy, ataxia, seizures, myoclonic seizures, pyramidal signs, dystonia, choria, muscle weakness, CPEO, ptosis, elevated alanine, abnormal EEG, MRS/lactate peak. 79% mtDNA copy number in blood. | | Mutations: | L304R, R1081P | | Age group: | childhood | | Age of Onset: n/a, Age of Patient: 10, Age of Death: n/a |
| Reference: | Navarro-Sastre et al, 2012; | | Description: | Alpers, psychomotor retardation, epileptic encephalopathy, progressive cerebral atrophy and altered liver enzymes, mtDNA depletion. Patient 9. Age of onset information obtained from corresponding author via email. | | Mutations: | G888D, L304R | | Age group: | infantile | | Age of Onset: 1, Age of Patient: n/a, Age of Death: 1.33 |
| Reference: | Navarro-Sastre et al, 2012; | | Description: | Alpers, intractable convulsions and severe epileptic status, high mtDNA depletion (8% residual mtDNA). Patient 10. Age of onset information obtained from corresponding author via email. | | Mutations: | L304R | | SNPs: | Y282D | | Age group: | infantile | | Age of Onset: 1.75, Age of Patient: n/a, Age of Death: n/a |
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| G737R | | | | Number of patients: (with G737R) | 13 | | Found together with: | | | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Wong et al, 2008; | | Description: | Onset 60 years with ataxia, neuropathy, myopathy, hearing loss, cerebellar atrophy, SANDO/SCAE, PEO. | | Mutations: | A467T, G737R | | Age group: | adult | | Age of Onset: 60, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Milone et al, 2011; | | Description: | progressive sensory ataxic neuropathy, ophthalmoparesis, cerebellar ataxia, limb weakness, muscle cramps, sensory hearing loss, dysarthria, dysphagia, constipation, and memory loss, brain MRI was abnormal with evidence of generalized cortical and cerebellar atrophy, evidence of a length-dependent sensory > motor polyneuropathy of axonal type, Multiple mtDNA deletions detected by PCR in blood | | Mutations: | A467T, G737R | | Age group: | adult | | Age of Onset: 53, Age of Patient: 58, Age of Death: n/a |
| Reference: | Horvath et al, 2006; | | Description: | Onset at 0.8 years with encephalopathy, liver dysfunction, diagnosed as Alpers. Death at 1 year. | | Mutations: | A767D, G737R | | Age group: | infantile | | Age of Onset: 0.8, Age of Patient: n/a, Age of Death: 1 |
| Reference: | Sitarz et al, 2014; | | Description: | Epilepsy, Myopathy. | | Mutations: | A767D, G737R | | Age group: | infantile | | Age of Onset: n/a, Age of Patient: 1, Age of Death: n/a |
Back to top | Reference: | Davidzon et al, 2006; | | Description: | Migraines in childhood, In 20s presented with peripheral sensory neuropathy and parkinsonisms. | | Mutations: | G737R, R853W | | Age group: | childhood | | Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Rempe et al, 2016; | | Description: | parkinsonism with dystonic toe and plantar flexion. Anxiety and generalized muscle weakness. Bilateral hypaesthesia of the lateral bottom of the foot and dorsal forefoot as well as bilateral distal pallhypaesthesia of the legs. Slight bilateral ptosis, slight axonal sensory polyneuropathy. | | Mutations: | G737R, R853W | | Age group: | adult | | Age of Onset: 27, Age of Patient: 32, Age of Death: n/a |
| Reference: | Harrower et al, 2008; | | Description: | Peripheral neuropathy, tremor, ataxia. | | Mutations: | G737R, R232H | | SNPs: | S64L | | Age group: | childhood | | Age of Onset: 10, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Tang et al, 2011; | | Description: | Muscle weakness, ptosis, ophthalmoparesis/CPEO. 61% mtDNA copy number in blood. | | Mutations: | G737R, L304R | | Age group: | adult | | Age of Onset: n/a, Age of Patient: 54, Age of Death: n/a |
| Reference: | Tang et al, 2011; | | Description: | Seizures, intractable seizures, abnormal EEG, abnormal MRI. 135% mtDNA copy number in blood. | | Mutations: | G426S, G737R | | Age group: | childhood | | Age of Onset: n/a, Age of Patient: 11, Age of Death: n/a |
Back to top | 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: | Hypoglycaemia, liver failure, seizures, developmental delay. 65% mtDNA copy number in muscle, ETC low. | | Mutations: | G737R, V855L | | Age group: | infantile | | Age of Onset: n/a, Age of Patient: 0.8, Age of Death: n/a |
| Reference: | Wong et al, 2008; | | Description: | Onset at age 3 with dementia,lactic acidosis, renal tubulopathy, dysmorphic features, cataract, short stature, myopathy. | | Mutations: | G737R, R943C | | SNPs: | E1143G | | Age group: | childhood | | Age of Onset: 3, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Tzoulis et al, 2009; | | Description: | PEO. Primary hypothyroidism and bilateral hearing loss of uncertain duration. She had been operated for bilateral ptosis at 75 years of age and presented to us with 2–3 years of worsening diplopia, gait unsteadiness and paresthaesiae in the distal lower limbs. asymmetrical ptosis and nearly complete external ophthalmoplegia with loss of convergence, oculocephalic reflex and Bell\'s reflex. She had symmetrical distal sensory loss in the lower limbs and absence of Achilles reflexes. | | Mutations: | G737R, W748S | | Age group: | adult | | Age of Onset: 75, Age of Patient: 86, 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 mutation G737R and a cluster 3 mutation: Age of onset information is extracted from a total of 1 patients and/ or patient families. | Age of onset | | |
1- 1- | 0
| 0
| 0
| 1
| | | infantile | childhd | juvenile | adult | | | 0% | 0% | 0% | 100% | |
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 G737R-cluster3 mutations | | Symptoms in patients with combination
G737R:cluster3 | | Muscle weakness | 100.0% | | Ptosis | 100.0% | | PEO | 100.0% |
| | Data gathered from clinical descriptions for 1 patient |
| | 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] |
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