Mutation Query
| | | | Allele 1: | S433C | | Allele 2: | E1143G | Allelic information known | | Refine query |
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| | | Residue S433 | | Cluster assignment: | | | Cluster description: | Polymerase active site and environs | | Subcluster: | 1C (residues 417-433) | | Subcluster description: | Mostly solvent exposed, contacts subclusters 1B, 1D, 1F, and 1G; equivalent to the G-helix of other family A polymerases | | POLG domain: | Exonuclease domain |
| Residue E1143 | | Cluster assignment: | | | Cluster description: | Single Nucleotide Polymorphism | | POLG domain: | Polymerase domain |
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Mutation Information
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| S433C | | | | Number of patients: (with S433C) | 1 | | Non-allelic with: | E1143G (100%) |  | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Hudson et al, 2006; | | Description: | PEO, ataxia, peripheral neuropathy, and episodes of encephalopathy. Asymptomatic mother had also S433C. | | Mutations: | S433C | | SNPs: | E1143G | | Age group: | unknown | | Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a |
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| E1143G | | | | Number of patients: (with E1143G) | 95 | | Found as the only mutation: | 1% of entries (1 patient) | | Found together with: | PNF=Putatively Non-Functional enzyme | | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Blok et al, 2009; | | Description: | Ptosis, CPEO, polyneuropathy, cerebellar ataxia, dysarthria. | | Mutations: | A467T, W748S | | SNPs: | E1143G | | Age group: | adult | | Age of Onset: n/a, Age of Patient: 47, Age of Death: n/a |
| Reference: | Ferrari et al, 2005; | | Description: | An apparently myogenic torticollis was noticed after a few months of life; at 10 months, he had two episodes of sudden head drop, followed by the onset of psychomotor arrest/ regression, hypotonia, ataxia and focal myoclonus of the right upper limb. In the following weeks, the myoclonus became subcontinuous, and was associated with rapidly progressive, severe generalized hypotonia and weakness requiring ventilatory assistance. Seizures were partially controlled with a combination of topiramate, clobazam and phenylbarbiturate. symmetrical lesions of the basal ganglia, thalami, cerebellar dentate nuclei and left occipital cortical and subcortical regions. abnormal accumulation of lactic acid in the putamen and a reduction of the N-acetyl aspartate. cholestatic jaundice, hypoglycaemia and hypocoagulation. The diagnostic conclusion was Alpers syndrome. | | Mutations: | W748S | | SNPs: | E1143G, PNF | | Age group: | infantile | | Age of Onset: 0.2, Age of Patient: n/a, Age of Death: 2.5 |
| Reference: | Ferrari et al, 2005; | | Description: | disease-free interval in the first 4 months after birth, followed by persistent vomiting, epileptic crises with loss of eye contact, and myoclonus in the upper limbs with secondary generalization and loss of consciousness. Persistent myoclonus in the upper limbs was associated with profound hypotonia and loss of eye contact. cortical atrophy and leukoencephalopathy in the subcortical areas of the frontal lobes. progressive hepatic failure with enlarged liver, hypoalbuminaemia and predominantly cholestatic jaundice led to the death of the child at 8 months of age. | | Mutations: | W748S | | SNPs: | E1143G, PNF | | Age group: | infantile | | Age of Onset: 0.3, Age of Patient: n/a, Age of Death: 0.67 |
| Reference: | Isohanni et al, 2011; | | Description: | Partial status epilepticus, epilepsia partialis, continua, hemiparesis, myoclonus, loss of vision, optical atrophy, pschomotor regression, liver dysfunction, death via pneumonia. | | Mutations: | G848S, W748S | | SNPs: | E1143G | | Age group: | infantile | | Age of Onset: 1, Age of Patient: n/a, Age of Death: 11 |
Back to top | Reference: | Isohanni et al, 2011; | | Description: | developmental delay, vomiting, partial status epilepticus, epilepsia partialis continua, myoclonus, ataxia, alive at age 3. | | Mutations: | T914P, W748S | | SNPs: | E1143G | | Age group: | infantile | | Age of Onset: 2.5, Age of Patient: 3, Age of Death: n/a |
| Reference: | Isohanni et al, 2011; | | Description: | epilepsy, vomiting, lowered consciousness, partial status epilepticus, epilepsia partialis continua, myoclonus, pschomotor regression, liver failure before valproate treatment, death via pneumonia. 72-76% mtDNA copy number in muscle. | | Mutations: | R807C, W748S | | SNPs: | E1143G | | Age group: | infantile | | Age of Onset: 1, Age of Patient: n/a, Age of Death: 3 |
| Reference: | Kollberg et al, 2006; | | Description: | Alpers, age of onset 6 months, age of death 13 months. 41% mtDNA copy number. During the first 6 months of life, he was considered healthy, but was irritable with colic-like symptoms. failure to thrive, delayed motor development. myoclonus. leftsided hemiparesis. | | Mutations: | R232H, W748S | | SNPs: | E1143G | | Age group: | infantile | | Age of Onset: 0.5, Age of Patient: n/a, Age of Death: 1.08 |
| Reference: | Kollberg et al, 2006; | | Description: | Ragged Red Fibers, COX-Deficient Fibers. mtDNA depletion. He was healthy and his development was normal until 5 months of age. He developed failure to thrive and muscular hypotonia. At 4 years of age, he developed myoclonus, which was first limited to the right eye and the right side of the mouth, but then progressed to epilepsia partialis continua of the entire left side of the body without loss of consciousness. He has developed a complex movement disorder and cognitive impairment, but contact, speech, and memory functions have been retained. He also had ptosis and uncontrolled and uncoordinated movements, especially in his arms. | | Mutations: | E1163G, W748S | | SNPs: | E1143G | | Age group: | infantile | | Age of Onset: 0.417, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Kollberg et al, 2006; | | Description: | Started as an ataxic syndrome, Alpers, ragged red fibers, COX-deficient fibers, mtDNA deletions. mtDNA copy numbers 1.6 fold. She was healthy and developed normally until her late preschool years when she developed slowly progressive ataxia. Occasional myoclonic seizures, and at 13 years of age, valproate treatment was started because of occipital seizures. ataxia, dementia, and cortical blindness. She developed refractory seizures, including multifocal EPC, status epilepticus, and myoclonus. | | Mutations: | A467T, W748S | | SNPs: | E1143G | | Age group: | childhood | | Age of Onset: 5, Age of Patient: 13, Age of Death: 14 |
Back to top | Reference: | Kollberg et al, 2006; | | Description: | psychomotor regression, refractory seizures, stroke-like episodes, hepatopathy, and ataxia. COX-deficient muscle fibers, mtDNA deletions, 160% mtDNA copy number. He was normal until 11 years of age when he developed mild tremor and ataxia. At 13 years of age, he reported occasional migraine-like headaches and was found to have mild ataxia and myoclonus. generalized seizures. mild leftsided hemiparesis, external ophthalmoplegia, and peripheral neuropathy. | | Mutations: | A467T, W748S | | SNPs: | E1143G | | Age group: | childhood | | Age of Onset: 11, Age of Patient: 24, Age of Death: n/a |
| 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: | Sarzi et al, 2007; | | Description: | Myoclonus, epilepsy, Psychomotor retardation, Alpers syndrome, steatosis | | Mutations: | W748S | | SNPs: | E1143G, PNF | | Age group: | infantile | | Age of Onset: 0.25, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Sarzi et al, 2007; | | Description: | Onset with walking difficulties, seizures at 2.5 years, hepatocellular insufficiency after valproate treatment, alpers syndrome, Liver mtDNA depletion. | | Mutations: | W748S | | SNPs: | E1143G | | Age group: | infantile | | Age of Onset: 2, Age of Patient: n/a, Age of Death: 3 |
| 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: | Taanman et al, 2009; | | Description: | Hypotonia at 8 weeks, seizures, hepatopathy, lactic acidemia, died of liver failure. 9% mtDNA copy number in muscle, 11% mtDNA copy number in liver. | | Mutations: | H1110Y, W748S | | SNPs: | E1143G, Q1236H | | Age group: | infantile | | Age of Onset: 0.1, Age of Patient: n/a, Age of Death: 0.8 |
| Reference: | Taanman et al, 2009; | | Description: | Onset at 6.5 years with alpers syndrome and death at 7.8 years. 23% mtDNA copy number in liver. | | Mutations: | G848S, W748S | | SNPs: | E1143G | | Age group: | childhood | | Age of Onset: 6.5, Age of Patient: n/a, Age of Death: 7.8 |
| Reference: | Winterthun et al, 2005; | | Description: | Ataxia, sensory ataxia, dysarthria, nystagmus, cognitive dysfunction, axonal neuropathy, demyelinating neuropathy. This man presented at age 26 with unsteadiness. Examination showed an ataxic gait, cerebellar dysarthria, myoclonic jerks of his head and facial muscles, mild limitation of horizontal eye movement, and horizontal nystagmus in the direction of gaze, with an additional vertical element when looking down. There were distal amyotrophy, absent reflexes in the legs, and a symmetric loss of all sensory modalities below the knee. Romberg’s test was positive. Episodes of depression. At age 31 he has an almost complete ophthalmoplegia, cerebellar dysarthria, myoclonus involving face and arms, truncal ataxia, and symmetric dysmetria. | | Mutations: | Q497H, Q497H, W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | adult | | Age of Onset: 23, Age of Patient: 38, Age of Death: n/a |
| Reference: | Winterthun et al, 2005; | | Description: | Headaches, a focal epilepsy with secondary generalisation, occipital epilepsy, dysarthria, nystagmus, cognitive dysfunction. Demyelinating neuropathy, axonal neuropathy. headaches preceded by visual symptoms, nausea, vomiting, and unsteadiness diagnosed as migraine. Shortly after, she had the first of a series of tonic-clonic seizures preceded by headache. Examination showed horizontal and vertical nystagmus, gait ataxia. | | Mutations: | Q497H, Q497H, W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | juvenile | | Age of Onset: 15, Age of Patient: 18, Age of Death: n/a |
| Reference: | Wong et al, 2008; | | Description: | Hearing loss, Ataxia Neuropathy Spectrum, Seizures, dementia, developmental delay | | Mutations: | A467T, Q497H, W748S | | SNPs: | E1143G | | Age group: | juvenile | | Age of Onset: 17, Age of Patient: n/a, Age of Death: n/a |
Back to top | Reference: | Wong et al, 2008; | | Description: | Muscle weakness, respiratory failure, Alpers, Lactic acidosis, Seizures, Demential , developmental delay | | Mutations: | W748S | | SNPs: | E1143G, PNF | | Age group: | childhood | | Age of Onset: 4, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Wong et al, 2008; | | Description: | Onset 33 years with neuropathy, myopathy, SANDO, lactic acidosis, PEO. | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | adult | | Age of Onset: 33, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Wong et al, 2008; | | Description: | developmental delay, dementia, seizures, Alpers, Family history of Alpers syndrome. | | Mutations: | G848S, Q497H, W748S | | SNPs: | E1143G | | Age group: | infantile | | Age of Onset: 1, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Zsurka et al, 2008; | | Description: | Epilepsy, seizures, VPA induced liver failure. | | Mutations: | L752P, W748S | | SNPs: | E1143G | | Age group: | childhood | | Age of Onset: 7, Age of Patient: n/a, Age of Death: 10 |
| Reference: | Davidzon et al, 2005; | | Description: | hepatocerebral syndrome, alpers, developmental delay, seizures, and hepatopathy leading to liver failure, liver mtDNA depletion | | Mutations: | G848S, W748S | | SNPs: | E1143G | | Age group: | infantile | | Age of Onset: 0.7, Age of Patient: n/a, Age of Death: 2.5 |
Back to top | Reference: | Davidzon et al, 2005; | | Description: | hepatocerebral syndrome, alpers, developmental delay, seizures, and hepatopathy leading to liver failure, liver mtDNA depletion, microvesicular steatosis, | | Mutations: | G848S, W748S | | SNPs: | E1143G | | Age group: | infantile | | Age of Onset: 1, Age of Patient: n/a, Age of Death: 6.5 |
| Reference: | Davidzon et al, 2005; | | Description: | hepatocerebral syndrome, alpers, developmental delay, seizures, and hepatopathy leading to liver failure, liver mtDNA depletion, microvesicular steatosis. | | Mutations: | G848S, W748S | | SNPs: | E1143G | | Age group: | infantile | | Age of Onset: 0.1, Age of Patient: n/a, Age of Death: 0.9 |
| Reference: | Davidzon et al, 2005; | | Description: | hepatocerebral syndrome, alpers, developmental delay, seizures, and hepatopathy leading to liver failure, microvesicular steatosis, fibrosis | | Mutations: | G848S, W748S | | SNPs: | E1143G | | Age group: | infantile | | Age of Onset: 0.3, Age of Patient: n/a, Age of Death: 1 |
| Reference: | Nguyen et al, 2005; | | Description: | Refractory seizures, psychomotor regression, liver disease, presenting symptom was status epilepticus, Transient hypoglycemia, Transient lactic acidemia | | Mutations: | G848S, W748S | | SNPs: | E1143G | | Age group: | infantile | | Age of Onset: 1, Age of Patient: n/a, Age of Death: 1.7 |
| Reference: | Milone et al, 2011; | | Description: | Stiffness, cramping of the lower extremities, foot numbness, and poor balance. The past medical history was significant for hypogonadotropic hypogonadism diagnosed 10 years prior. ophthalmoplegia without ptosis, mild lower proximal weakness, Multiple mtDNA deletions detected by PCR in muscle | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | adult | | Age of Onset: 32, Age of Patient: 33, Age of Death: n/a |
Back to top | Reference: | Milone et al, 2011; | | Description: | progressive unsteadiness,limb paresthesias, dysarthria, dysphagia, and weakness, ophthalmoparesis,dysarthria, palatal tremor, moderate axial and appendicular ataxia, and distal pan-modality sensory loss | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | adult | | Age of Onset: 32, Age of Patient: 33, Age of Death: n/a |
| Reference: | Komulainen et al, 2010; | | Description: | mental retardation, psychiatric symptoms, mild bilateral ptosis and epilepsy, Seizures occurred at age 11 years, and focal generalized epilepsy was diagnosed. | | Mutations: | W748S | | SNPs: | E1143G, R722H | | Age group: | childhood | | Age of Onset: 11, Age of Patient: 22, Age of Death: n/a |
| Reference: | Mousson de Camaret et al, 2011 | | Description: | At 16 months of age, he started a severe status epilepticus. Cerebral MRI showed brain cortical atrophy. he developed intractable epileptic encephalopathy associated with generalized hypotonia and cortical blindness. diffuse hypotonia, lethargy and vomiting. During the two following years, epilepsy was always very active including spasms and myoclonic jerks. progressive hepatic failure. Alpers. | | Mutations: | W748S | | SNPs: | E1143G, PNF | | Age group: | infantile | | Age of Onset: 1.33, Age of Patient: n/a, Age of Death: 4.17 |
| 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: | Hakonen et al, 2005; | | Description: | Onset with balance disturbances and neuropathy, Gait and limb ataxia, Dysarthria, restricted eye movements, ptosis, Cognitive impairment, Obesity, cramps, sensory motor polyneuropathy | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | adult | | Age of Onset: 38, Age of Patient: 44, Age of Death: n/a |
Back to top | Reference: | Hakonen et al, 2005; | | Description: | Onset with balance disturbances and neuropathy, Gait and limb ataxia, Myoclonus, tremor, Dysarthria, restricted eye movements, Cognitive impairment, Psychiatric symptoms, Obesity, sensory motor polyneuropathy | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | adult | | Age of Onset: 38, Age of Patient: 51, Age of Death: n/a |
| Reference: | Hakonen et al, 2005; | | Description: | Onset with balance disturbances and neuropathy, Gait and limb ataxia, tremor, Involuntary movements, Dysarthria, Dysphagia, Nystagmus, restricted eye movements, Psychiatric symptoms, Muscle strength decreased, Obesity, muscle cramps, amyotrophy, pes cavus, sensory motor polyneuropathy | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | adult | | Age of Onset: 27, Age of Patient: 38, Age of Death: n/a |
| Reference: | Hakonen et al, 2005; | | Description: | Onset with balance disturbances, Gait and limb ataxia, Dysarthria, Dysphagia, Nystagmus, diplopia, Cognitive impairment, Muscle strength decreased, sensory neural hearing deficit, sensory motor polyneuropathy | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | adult | | Age of Onset: 32, Age of Patient: 46, Age of Death: n/a |
| Reference: | Hakonen et al, 2005; | | Description: | Onset with balance disturbances, Gait and limb ataxia, facial Involuntary movements, Dysarthria, Dysphagia, Nystagmus, other eye-movement abnormalities, Psychiatric symptoms, premature menopause, Obesity, sensory motor polyneuropathy | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | adult | | Age of Onset: 27, Age of Patient: 42, Age of Death: n/a |
| Reference: | Hakonen et al, 2005; | | Description: | Onset with epilepsy, Gait and limb ataxia, Epilepsy, Dysarthria, Nystagmus, diplopia, Psychiatric symptoms, Obesity, sensory motor polyneuropathy | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | adult | | Age of Onset: 24, Age of Patient: 55, Age of Death: n/a |
Back to top | Reference: | Hakonen et al, 2005; | | Description: | Onset with epilepsy, Gait and limb ataxia, Epilepsy, Myoclonus, facial Involuntary movements, Dysarthria, Dysphagia, Nystagmus, other eye-movement abnormalities, Cognitive impairment, Psychiatric symptoms, Muscle strength decreased, Obesity | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | juvenile | | Age of Onset: 16, Age of Patient: 37, Age of Death: n/a |
| Reference: | Hakonen et al, 2005; | | Description: | Onset with epilepsy, Gait and limb ataxia, Epilepsy, Myoclonus, head tremor, Dysarthria, other eye-movement abnormalities, Nystagmus, Cognitive impairment, Psychiatric symptoms, cramps, sensory motor polyneuropathy | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | adult | | Age of Onset: 23, Age of Patient: 45, Age of Death: n/a |
| Reference: | Hakonen et al, 2005; | | Description: | Onset with epilepsy, Gait and limb ataxia, Epilepsy, Myoclonus, head tremor, facial Involuntary movements, Dysarthria, Nystagmus, other eye-movement abnormalities, Cognitive impairment, Psychiatric symptoms, cramps | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | juvenile | | Age of Onset: 17, Age of Patient: 45, Age of Death: n/a |
| Reference: | Hakonen et al, 2005; | | Description: | Onset with epilepsy, Gait and limb ataxia, Myoclonus, Involuntary movements, Dysarthria, Dysphagia, Nystagmus, other eye-movement abnormalities, Cognitive impairment, Obesity, sensory neural hearing deficit, sensory motor polyneuropathy | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | juvenile | | Age of Onset: 19, Age of Patient: 44, Age of Death: n/a |
| Reference: | Hakonen et al, 2005; | | Description: | Onset with headaches, Gait and limb ataxia, Epilepsy, Myoclonus, Involuntary movements, Dysarthria, Dysphagia, Nystagmus, other eye-movement abnormalities, restricted eye movements, ptosis, Cognitive impairment, Psychiatric symptoms, Muscle strength decreased, Obesity | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | adult | | Age of Onset: 28, Age of Patient: 51, Age of Death: n/a |
Back to top | Reference: | Hakonen et al, 2005; | | Description: | Onset with neuropathy, Gait and limb ataxia, Dysarthria, Dysphagia, other eye-movement abnormalities, Cognitive impairment, Psychiatric symptoms, Obesity, sensory motor polyneuropathy | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | adult | | Age of Onset: 41, Age of Patient: 58, Age of Death: n/a |
| Reference: | Hakonen et al, 2005; | | Description: | Onset with neuropathy, Gait and limb ataxia, tremor, Dysarthria, Nystagmus, Psychiatric symptoms, Muscle strength decreased, amyotrophy, pes cavus, sensory motor polyneuropathy | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | adult | | Age of Onset: 36, Age of Patient: 51, Age of Death: n/a |
| Reference: | Hakonen et al, 2005; | | Description: | Onset with tremor, Gait and limb ataxia, Epilepsy, Myoclonus, Involuntary movements, Dysarthria, eye muscle weakness, Cognitive impairment, Psychiatric symptoms, Muscle strength decreased. | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | childhood | | Age of Onset: 5, Age of Patient: n/a, Age of Death: 35 |
| Reference: | Tzoulis et al, 2006; | | Description: | Presented with epilepsy and headaches, ataxia, status epilepticus, nystagmus, myoclonus, neuropathy. Sodium valproate treatment 6 weeks prior to death. Liver dysfunction, cause of death status epilepticus and liver failure. Hepatic histology showed acute liver necrosis. | | Mutations: | A467T, W748S | | SNPs: | E1143G | | Age group: | juvenile | | Age of Onset: 19, Age of Patient: n/a, Age of Death: 19 |
| Reference: | Tzoulis et al, 2006; | | Description: | Presented with epilepsy and headaches, ataxia, epilepsy, status epilepticus, myoclonus, neuropathy. Sodium valproate treatment 7 weeks prior to death. Liver dysfunction and rising liver enzymes and bilirubin terminally, cause of death status epilepticus. Hepatic histology showed centrolobular degeneration. | | Mutations: | A467T, W748S | | SNPs: | E1143G | | Age group: | juvenile | | Age of Onset: 14, Age of Patient: n/a, Age of Death: 23 |
Back to top | Reference: | Tzoulis et al, 2006; | | Description: | Presented with epilepsy, ataxia, nystagmus, neuropathy, ptosis/ PEO onset at age 65 | | Mutations: | W748S | | SNPs: | E1143G | | Age group: | adult | | Age of Onset: 55, Age of Patient: 74, Age of Death: n/a |
| Reference: | Tzoulis et al, 2006; | | Description: | Presented with epilepsy, ataxia, status epilepticus, headaches, myoclonus, neuropathy | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | juvenile | | Age of Onset: 18, Age of Patient: 19, Age of Death: n/a |
| Reference: | Tzoulis et al, 2006; | | Description: | Presented with epilepsy, ataxia, status epilepticus, headaches, myoclonus, neuropathy, ptosis/ PEO onset at age 28. Acute liver failure after 4 months of sodium valproate treatment | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | juvenile | | Age of Onset: 19, Age of Patient: 33, Age of Death: n/a |
| Reference: | Tzoulis et al, 2006; | | Description: | Presented with epilepsy, ataxia, status epilepticus, headaches, myoclonus, neuropathy. Sodium valproate treatment for 8 months. Stopped just prior to death. Liver dysfunction, cause of death liver failure. Hepatic histology showed acute liver necrosis. | | Mutations: | A467T, W748S | | SNPs: | E1143G | | Age group: | childhood | | Age of Onset: 10, Age of Patient: n/a, Age of Death: 10 |
| Reference: | Tzoulis et al, 2006; | | Description: | Presented with epilepsy, ataxia, status epilepticus, headaches, nystagmus, myoclonus, neuropathy, treatment with sodium valproate for 2 months, died 3 years later due to status epilepticus, disseminated intravascular coagulation, liver failure. | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | childhood | | Age of Onset: 10, Age of Patient: n/a, Age of Death: 22 |
Back to top | Reference: | Tzoulis et al, 2006; | | Description: | Presented with epilepsy, headaches, epilepsy, status epilepticus, headaches, nystagmus, and neuropathy. Sodium valproate treatment for 2 months then stopped 2 months prior to death. Liver dysfunction, liver transplant 1 month prior to death, cause of death liver failure. Hepatic histology showed acute liver necrosis. | | Mutations: | A467T, W748S | | SNPs: | E1143G | | Age group: | adult | | Age of Onset: 20, Age of Patient: n/a, Age of Death: 20 |
| Reference: | Tzoulis et al, 2006; | | Description: | Presented with epilepsy, status epilepticus, headaches, nystagmus, myoclonus, neuropathy. Sodium valproate treatment 7 weeks prior to death. Liver dysfunction and rising liver enzymes and bilirubin terminally, cause of death status epilepticus. Hepatic histology showed centrolobular degeneration. | | Mutations: | A467T, W748S | | SNPs: | E1143G | | Age group: | juvenile | | Age of Onset: 15, Age of Patient: n/a, Age of Death: 21 |
| Reference: | Tzoulis et al, 2006; | | Description: | Presented with epilepsy, status epilepticus, nystagmus, neuropathy | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | juvenile | | Age of Onset: 17, Age of Patient: 18, Age of Death: n/a |
| Reference: | Tzoulis et al, 2006; | | Description: | Presented with migraine like headaches, ataxia, epilepsy, status epilepticus, nystagmus, myoclonus, neuropathy, ptosis/ PEO onset at age 26 | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | juvenile | | Age of Onset: 17, Age of Patient: 38, Age of Death: n/a |
| Reference: | Tzoulis et al, 2006; | | Description: | Presented with migraine like headaches, ataxia, epilepsy, status epilepticus, nystagmus, myoclonus, neuropathy. Sodium valproate treatment 3 months prior to death. Liver dysfunction and rising liver enzymes and bilirubin terminally, cause of death status epilepticus and multi-organ failure. Acute liver necrosis | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | childhood | | Age of Onset: 8, Age of Patient: n/a, Age of Death: 9 |
Back to top | Reference: | Tzoulis et al, 2006; | | Description: | Presented with migraine like headaches, ataxia, epilepsy, status epilepticus, nystagmus, neuropathy | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | juvenile | | Age of Onset: 17, Age of Patient: 27, Age of Death: n/a |
| Reference: | Tzoulis et al, 2006; | | Description: | Presented with migraine like headaches, ataxia, nystagmus, neuropathy, PEO/ Ptosis onset age >30 | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | childhood | | Age of Onset: 12, Age of Patient: 38, Age of Death: n/a |
| Reference: | Tzoulis et al, 2006; | | Description: | Presented with progressive gait unsteadiness and headaches, ataxia, epilepsy, status epilepticus, nystagmus, neuropathy. Died 2 months after treatment with sodium valproate, cause of death status epilepticus | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | juvenile | | Age of Onset: 15, Age of Patient: n/a, Age of Death: 57 |
| Reference: | Tzoulis et al, 2006; | | Description: | Presented with progressive gait unsteadiness, ataxia, epilepsy, status epilepticus, headaches, myoclonus, neuropathy, ptosis/ PEO onset age 30. Mild liver dysfunction. Cause of death status epilepticus. | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | childhood | | Age of Onset: 4, Age of Patient: n/a, Age of Death: 30 |
| Reference: | Tzoulis et al, 2006; | | Description: | Presented with progressive gait unsteadiness, ataxia, headaches, myoclonus, neuropathy, PEO, ptosis onset at age 44 | | Mutations: | A467T, W748S | | SNPs: | E1143G | | Age group: | adult | | Age of Onset: 36, Age of Patient: 50, Age of Death: n/a |
Back to top | Reference: | Tzoulis et al, 2006; | | Description: | Presented with progressive gait unsteadiness, ataxia, headaches, neuropathy, PEO ptosis onset age 25 | | Mutations: | A467T, W748S | | SNPs: | E1143G | | Age group: | adult | | Age of Onset: 24, Age of Patient: 43, Age of Death: n/a |
| Reference: | Tzoulis et al, 2006; | | Description: | Presented with speech delay, ataxia, epilepsy, status epilepticus, and headaches. Liver dysfunction and rising liver enzymes and bilirubin terminally, cause of death status epilepticus, multi-organ failure. Hepatic histology showed marked steatosis. | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | childhood | | Age of Onset: 8, Age of Patient: n/a, Age of Death: 9 |
| Reference: | Paus et al, 2008; | | Description: | Presented with PEO, mild bilateral ptosis, dysarthria, ataxia, and neuropathy | | Mutations: | A467T, W748S | | SNPs: | E1143G | | Age group: | adult | | Age of Onset: 36, Age of Patient: 37, Age of Death: n/a |
| Reference: | Remes et al, 2008; | | Description: | patient noticed gait and balance difficulties at age 46 years, ataxia, CPEO, cortical and cerebellar atrophy, axonal sensory polyneuropathy, Symmetrical bradykinesia and rigidity, mild tremor, paranoid delusions, During the last 2 years of life he had marked rigidity, dysphagia, myoclonic jerks and dystonia | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | adult | | Age of Onset: 46, Age of Patient: 65, Age of Death: n/a |
| Reference: | Uusimaa et al, 2008; | | Description: | Headache, visual symptoms, migraine-like headache, Athetosis, nystagmus, emiparesis, valproic acid induced Liver failure, sepsis, pancreatitis, status epilepticus | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | juvenile | | Age of Onset: 14, Age of Patient: 15, Age of Death: n/a |
Back to top | Reference: | Uusimaa et al, 2008; | | Description: | Migraine like headaches, visual symptoms, focal generalized seizures, severe liver failure, valproate induced liver failure | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | juvenile | | Age of Onset: 15, Age of Patient: n/a, Age of Death: 20 |
| Reference: | Uusimaa et al, 2008; | | Description: | Seizures, status epilepticus, visual symptoms, nystagmus, valproic acid induced liver failure | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | juvenile | | Age of Onset: 17, Age of Patient: 21, Age of Death: n/a |
| Reference: | Amiot et al, 2009; | | Description: | Peripheral neuropathy, PEO, ataxia, hearing loss, dysarthria-dysphonia, urinary tract involvement | | Mutations: | A143V, W748S | | SNPs: | E1143G | | Age group: | adult | | Age of Onset: 40, Age of Patient: 49, Age of Death: n/a |
| Reference: | Palin et al, 2012; | | Description: | Gait disturbance since childhood. Early onset suggested anticipation. In his 20's he developed photophobia and general clumsiness and benign paroxysmal positional vertigo. From the age of 37 he has had unspecific sensory polyneuropathy, confirmed by electromyography. He had several simple partial seizures at the age of 39, and has mild anxiety and depression. | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | childhood | | Age of Onset: 5, Age of Patient: 41, Age of Death: n/a |
| Reference: | Palin et al, 2012; | | Description: | No neurological symptoms, but type-2 diabetes and hypertension. | | Mutations: | W748S | | SNPs: | E1143G | | Age group: | adult | | Age of Onset: n/a, Age of Patient: 63, Age of Death: n/a |
Back to top | Reference: | Palin et al, 2012; | | Description: | developed gait disturbance by the age of 35, progressing to increasing clumsiness in lower extremities, dysarthria, diplopia, and occasional amnesia at the age of 44. She developed ataxia, slight polyneuropathy, and external ophthalmoplegia. At the age of 46 she had slightly increased plasma creatine kinase levels and symmetrical cerebellar peduncular white matter signal intensity increase in brain MRI. The first epileptic seizure, requiring treatment by general anesthesia, oc- curred at the age of 55, after which she was hospitalized permanently. From her 30's, she received psychiatric care due to anxiety and depression. A neuropsychological examination revealed decrease in visual reasoning and memory functions. She deceased at the age of 56 due to pneumonia and pulmonary embolism. | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | adult | | Age of Onset: 35, Age of Patient: n/a, Age of Death: 56 |
| Reference: | Posada et al, 2010; | | Description: | Ataxic sensory neuropathy, dysarthria, progressive ophthalmoplegia, paresthesia of lower extremities, unsteady gait, slurred speech, absent deep tendon reflexes, vibrations, ataxic gait and positive Romberg sign. Multiple mtDNA deletions, a marked decrease in mtDNA copy number. | | Mutations: | A467T, W748S | | SNPs: | E1143G | | Age group: | adult | | Age of Onset: 37, Age of Patient: 47, 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: | Brunetti-Pierri et al, 2008; | | Description: | He exhibited a very similar phenotype to his sister, with a catastrophic onset of intractable seizures at the age of 9 months, progressive encephalopathy with epilepsia partialis continua and myoclonic jerks, and developmental regression. MRI imaging was not performed. | | Mutations: | G848S, Q497H, W748S | | SNPs: | E1143G | | Age group: | infantile | | Age of Onset: 0.5, Age of Patient: 1.25, Age of Death: n/a |
| Reference: | Brunetti-Pierri et al, 2008; | | Description: | He exhibited a very similar phenotype to his sister, with a catastrophic onset of intractable seizures at the age of 9 months, progressive encephalopathy with epilepsia partialis continua and myoclonic jerks, and developmental regression. MRI imaging was not performed. | | Mutations: | G848S, Q497H, W748S | | SNPs: | E1143G | | Age group: | infantile | | Age of Onset: 0.5, Age of Patient: 1.25, Age of Death: n/a |
Back to top | Reference: | Brunetti-Pierri et al, 2008; | | Description: | The index patient presented at the age of 8 months with microcephaly, seizures, and developmental delay. From the time of the first observation she rapidly developed epilepsia partialis continua, multifocal myoclonic jerks, and progressive psychomotor retardation. MRI performed at 8 months was generally unremarkable. By 9 months of age the brain MRI showed signifi cant changes including a diffuse severe cerebral and cerebellar atrophy involving gray and white matter. | | Mutations: | G848S, Q497H, W748S | | SNPs: | E1143G | | Age group: | infantile | | Age of Onset: n/a, Age of Patient: 0.6, Age of Death: 1 |
| Reference: | Ylönen et al, 2013; | | Description: | late-onset parkinsons. Tremor. Cardiac arrhythmia. | | Mutations: | W748S | | SNPs: | E1143G, R993C | | Age group: | adult | | Age of Onset: 72, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Van Goethem et al, 2004; | | Description: | minor tremor of the hands from age 12 years. In his late 20s, he experienced tingling in both hands, followed by tingling in the legs. In the early fourth decade, he became unsteady at walking, especially in the dark. From his early 40s, his speech became slurred (dysarthria). On examination at age 52 years, he had an ataxic gait, and Romberg test was positive. There was dysarthria and bilateral ophthalmoparesis. generalized areflexia. | | Mutations: | A467T, W748S | | SNPs: | E1143G | | Age group: | childhood | | Age of Onset: 12, Age of Patient: 52, Age of Death: n/a |
| Reference: | Van Goethem et al, 2004; | | Description: | plurimetabolic syndrome. At age 30 years, he noted disturbed balance, and ataxia and severe axonal neuropathy were diagnosed. On examination at age 32 years, he had slowed ocular pursuit movements but with full range of motion. He had severe gait ataxia, imbalance, and trunk ataxia, as well as clumsiness of the hands. Achilles tendon reflexes were absent. dysarthria, obesity, chronic motor axonopathy, moderate sensory neuropathy at the upper limbs, mild neurogenic atrophy. | | Mutations: | W748S, W748S | | SNPs: | E1143G, E1143G | | Age group: | adult | | Age of Onset: 30, Age of Patient: 33, Age of Death: n/a |
| Reference: | Janssen et al, 2016; | | Description: | Focal seizures with left visual field symptoms and motor signs. Neurological examination disclosed PEO, dysarthria, decreased reflexes, loss of proprioception distally in the legs, discrete pyramidal signs and appendicular ataxia on the left side with an ataxic gait. Mild cognitive decline was present. infratentorial white matter lesions, axonal polyneuropathy. negative myoclonus. | | Mutations: | W748S, W748S | | SNPs: | E1143G | | Age group: | adult | | Age of Onset: 26, Age of Patient: 28, Age of Death: 33.5 |
Back to top | Reference: | Janssen et al, 2016; | | Description: | Migraine, ataxia, polyneuropathy. focal seizures with visual symptoms and motor signs, and secondary generalized tonic-clonic seizure. Clinical neurological examination revealed an ataxic gait and areflexia with sensory loss. Convulsive status epilepticus. Cerebral MRI revealed a left occipital and left thalamic lesion. | | Mutations: | A467T, W748S | | SNPs: | E1143G | | Age group: | juvenile | | Age of Onset: 17, Age of Patient: 20, Age of Death: 23 |
| Reference: | Janssen et al, 2016; | | Description: | Presented with status epilepticus, occipital lobe seizures. Further neurologic examination showed ataxic gait and appendicular ataxia. chronic sensory axonal polyneuropathy. Cognitive decline. At follow-up consultation 6 months after the initial presentation, she had not experienced any more seizures. | | Mutations: | A467T, W748S | | SNPs: | E1143G | | Age group: | juvenile | | Age of Onset: 18, Age of Patient: 18.7, Age of Death: n/a |
| Reference: | Simonati et al, 2003b; | | Description: | epilepsia partialis continua at 10 months, pyramido-cerebellar syndrome 19 months, myoclonic seizures when 4.5 years old. myoclonic jerks. At the age of 8 years, a brain CT scan showed atrophy of the right occipital cortex. signs and symptoms of liver dysfunction. chronic progressive liver disease. diffuse cortical atrophy. myoclonic epilepsy became resistant to any medication, myoclonic status along with episodes of respiratory failure. His clinical condition rapidly worsened and led to a vegetative state. | | Mutations: | L244P, W748S | | SNPs: | E1143G | | Age group: | infantile | | Age of Onset: 0.8, Age of Patient: 9, Age of Death: 15 |
| Reference: | Simonati et al, 2003b; | | Description: | myoclonic fits of the right limbs and then a dystonic-ataxic syndrome at the age of 5 months. He had a rapid clinical deterioration. At age 6 months, a brain CT scan showed diffuse cortical atrophy. acute hepatic failure. | | Mutations: | L244P, W748S | | SNPs: | E1143G | | Age group: | infantile | | Age of Onset: 0.42, Age of Patient: n/a, Age of Death: 1.1 |
| Reference: | Stewart et al, 2009; | | Description: | Ataxia, PEO, axonal neuropathy, cerebellar atrophy. 3% COX deficient fibers. | | Mutations: | G746S, G848S | | SNPs: | E1143G | | Age group: | juvenile | | Age of Onset: 16, Age of Patient: n/a, Age of Death: n/a |
Back to top | Reference: | Hisama et al, 2005; | | Description: | Presented with ataxia and transient diplopia at age 25 and showed ptosis, external ophthalmoplegia, nystagmus, had a mild tremor of outstretched hands, marked dysmetria, Romberg sign, severe ataxia, was unable to stand on one foot, multiple mtDNA deletions in muscle. | | Mutations: | A889T | | SNPs: | E1143G | | Age group: | adult | | Age of Onset: n/a, Age of Patient: 25, Age of Death: n/a |
| Reference: | Hisama et al, 2005; | | Description: | presented at age 7 years with gait difficulty and pes cavus. He developed upper extremity tremor, scanning speech, and horizontal nystagmus by age 15. at age 20 showed ptosis, external ophthalmoplegia, mildly decreased vibration and pin prick sensation, intention tremor, absent ankle and brachioradialis reflexes, and ataxic gait. Over the next 5 years, he experienced progression of the ptosis and ophthalmoplegia. The tremor became disabling at rest and with action, and he became wheelchair-dependent. | | Mutations: | A889T | | SNPs: | E1143G | | Age group: | childhood | | Age of Onset: 7, Age of Patient: 20, Age of Death: n/a |
| Reference: | McFarland et al, 2008; | | Description: | Presented with epilepsy following minor head trauma, 2 months after valproate treatment developed persistent vomiting and encephalopathy, deranged liver function tests, prolonged clotting, elevated ammonia, and a high plasma lactate, Hepatic dysfunction progressed, | | Mutations: | A467T, Q879H, T885S | | SNPs: | E1143G | | Age group: | infantile | | Age of Onset: 2, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Hudson et al, 2006; | | Description: | PEO, ataxia, peripheral neuropathy, and episodes of encephalopathy. Asymptomatic mother had also S433C. | | Mutations: | S433C | | SNPs: | E1143G | | Age group: | unknown | | Age of Onset: n/a, Age of Patient: n/a, 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 |
Back to top | Reference: | Luoma et al, 2007; | | Description: | Parkinsons disease, tremor, rigidity, hypo-/ bradykinesia. Also had Histiocytosis and breast cancer | | Mutations: | | | SNPs: | E1143G | | Age group: | adult | | Age of Onset: 47, Age of Patient: 67, Age of Death: n/a |
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The following information is based on PON-P2 mutation pathogenicity prediction software results. Cluster 1 mutation with a non-cluster-mapping mutation (SNP) E1143G | PON-P2 predictions results for E1143G | | Pathogenicity: | Neutral | | Probability: | 0.084 | | Standard Error: | 0.071 | | Prediction result is based on sequence analysis only and may not be accurate. |
Mutation pathogenicity prediction suggests mutation E1143G is non-pathogenic.
Predicted chance of pathogenicity is 8.4%. See further details for residue 1143. All mutations mapping into the pathogenic clusters are in high risk of being pathogenic. As a rule, a patient must have a pathogenic mutation in both of his/ her POLG genes to develop a POLG-related syndrome. |
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