Mutation Query
| | | | Allele 1: | Y955C | | Allele 2: | Q1236H | Allelic information known | | Refine query |
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| | | Residue Y955 | | 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 Q1236 | | Cluster assignment: | | | Cluster description: | Single Nucleotide Polymorphism | | POLG domain: | Polymerase domain |
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Mutation Information
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| Y955C | | | | Number of patients: (with Y955C) | 40 | | Found as the only mutation: | 95% of entries (38 patients) | | Non-allelic with: | Q1236H (3%) G517V (3%) |  | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Lamantea et al, 2002; | | Description: | PEO. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: n/a, Age of Patient: 31, Age of Death: n/a |
| Reference: | Lamantea et al, 2002; | | Description: | PEO. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: n/a, Age of Patient: 54, Age of Death: n/a |
| Reference: | Luoma et al, 2004; | | Description: | PEO, Parkinsons, rigidity, bradykinesia, ptosis, muscle weakness, cataracts, ataxia. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 35, Age of Patient: 60, Age of Death: n/a |
| Reference: | Luoma et al, 2004; | | Description: | PEO, Parkinsons, rigidity, resting tremor, bradykinesia, ptosis, muscle weakness, cataracts, ataxia. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 25, Age of Patient: 58, Age of Death: 60 |
Back to top | Reference: | Luoma et al, 2004; | | Description: | PEO, Primary amenorrhea, Parkinsons, resting tremor, rigidity, bradykinesia, ptosis, muscle weakness, mental retardation, cataracts, ataxia, head tremor | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 23, Age of Patient: 64, Age of Death: n/a |
| Reference: | Luoma et al, 2004; | | Description: | PEO, premature menopause, Parkinsons, resting tremor, rigidity, bradykinesia, ptosis, cataracts, ataxia. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 21, Age of Patient: 62, Age of Death: n/a |
| Reference: | Luoma et al, 2004; | | Description: | PEO, premature menupause, ptosis, muscle weakness, cataracts | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 30, Age of Patient: 52, Age of Death: n/a |
| Reference: | Luoma et al, 2004; | | Description: | PEO, ptosis, cataracts, rheumatoid arthritis, cardiac failure | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 40, Age of Patient: n/a, Age of Death: 67 |
| Reference: | Luoma et al, 2004; | | Description: | PEO, ptosis, muscle weakness | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 23, Age of Patient: 33, Age of Death: n/a |
Back to top | Reference: | Luoma et al, 2004; | | Description: | Parkinsons, resting tremor, ptosis, PEO, Muscle weakness, cataracts, Neuropathy | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 30, Age of Patient: 74, Age of Death: n/a |
| Reference: | Luoma et al, 2004; | | Description: | Parkinsons, resting tremor, rigidity, bradykinesia, ptosis, PEO, Muscle weakness, Neuropathy | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 49, Age of Patient: 50, Age of Death: n/a |
| Reference: | Luoma et al, 2004; | | Description: | Parkinsons, resting tremor, rigidity, bradykinesia, ptosis, PEO, Muscle weakness, cataracts, Neuropathy. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 49, Age of Patient: 73, Age of Death: n/a |
| Reference: | Luoma et al, 2004; | | Description: | Parkinsons, resting tremor, rigidity, bradykinesia, ptosis, PEO, muscle weakness, Cataracts, presbyacusis, ataxia, premature menopause, neuropathy. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 22, Age of Patient: 60, Age of Death: 61 |
| Reference: | Luoma et al, 2004; | | Description: | Parkinsons, rigidity, bradykinesia, ptosis, PEO, muscle weakness, hypoacusia, premature menopause. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 30, Age of Patient: 67, Age of Death: n/a |
Back to top | Reference: | Luoma et al, 2004; | | Description: | Ptosis, PEO, Exercise intolerance, pigmentary retinopathy, neuropathy | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 28, Age of Patient: 30, Age of Death: n/a |
| Reference: | Luoma et al, 2004; | | Description: | Resting tremor, rigidity, bradykinesia, ptosis, PEO, muscle weakness, periodic depression, dementia, cataracts, Parkinsons. | | Mutations: | Y955C | | Age group: | childhood | | Age of Onset: 10, Age of Patient: 58, Age of Death: 65 |
| Reference: | Luoma et al, 2004; | | Description: | ptosis, weak achilles tendon reflexes | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 33, Age of Patient: 38, Age of Death: n/a |
| Reference: | Tang et al, 2011; | | Description: | CPEO, myopathy. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: n/a, Age of Patient: 45, Age of Death: n/a |
| Reference: | Van Goethem et al, 2003a; | | Description: | CPEO, myopathy. Muscle biopsy showed RRF, multiple mtDNA deletions. Age of onset for three alcoholics ranged from 25-39, and age of death ranged from 54-65. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 25, Age of Patient: n/a, Age of Death: 54 |
Back to top | Reference: | Wong et al, 2008; | | Description: | Onset 0.1 years with dementia, liver dysfunction, lactic acidosis, hearing loss, failure to thrive, generalized ETC complex deficiency. | | Mutations: | Y955C | | Age group: | infantile | | Age of Onset: 0.1, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Kollberg et al, 2005; | | Description: | adPEO, multiple mtDNA deletions in muscle tissue. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 55, Age of Patient: 55, Age of Death: n/a |
| Reference: | Kollberg et al, 2005; | | Description: | adPEO, multiple mtDNA deletions in muscle tissue. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: n/a, Age of Patient: 53, Age of Death: n/a |
| Reference: | Kollberg et al, 2005; | | Description: | adPEO, multiple mtDNA deletions in muscle tissue. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: n/a, Age of Patient: 60, Age of Death: n/a |
| Reference: | Kollberg et al, 2005; | | Description: | adPEO, multiple mtDNA deletions in muscle tissue. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: n/a, Age of Patient: 60, Age of Death: n/a |
Back to top | Reference: | Pagnamenta et al, 2006; | | Description: | Presented with ptosis and PEO, in early 20’s, premature ovarian failure at 32 years, proximal muscle weakness, exertional dyspnoea and sensory ataxia, dysphagia. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 22, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Pagnamenta et al, 2006; | | Description: | Presented with ptosis and PEO, in early 20’s, premature ovarian failure at 35 years, proximal muscle weakness, exertional dyspnoea and sensory ataxia, dysphagia. At the age of 57, patient III-2 was noted to have a progressive, parkinsonian-like resting tremor and reduced rapid alternating movements affecting her left arm and leg, and mild bradykinesia. ragged-red fibres | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 22, Age of Patient: 57, Age of Death: n/a |
| Reference: | Mukai et al, 2013; | | Description: | gait instability, mild parkinsonian features, including cogwheel rigidity and bradykinesia. ragged-red fibers, decreased cytochrome c oxidase activity. Multiple mtDNA deletions were detected. PEO. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 65, Age of Patient: 69, Age of Death: n/a |
| Reference: | Mukai et al, 2013; | | Description: | rigidity with cogwheel phenomenon, bradykinesia, resting tremor and postural instability. Ragged-red fibers as well as fibers with increased subsarcolemmal succinate dehydrogenase activity and decreased cytochrome c oxidase activity. Multiple mtDNA deletions were detected. Parkinsons. PEO. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 60, Age of Patient: 73, Age of Death: n/a |
| Reference: | Van Goethem et al, 2001; | | Description: | Neuropathic symptoms, psychiatric symptoms, distal sensoral neuropathy, areflexia, pes cavus. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 28, Age of Patient: 29, Age of Death: n/a |
Back to top | Reference: | Van Goethem et al, 2001; | | Description: | Ocular symptoms, ptosis, Ophthalmoplegia, Muscle weakness, areflexia. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 30, Age of Patient: 52, Age of Death: n/a |
| Reference: | Van Goethem et al, 2001; | | Description: | Ocular symptoms, ptosis, Ophthalmoplegia, Muscle weakness, areflexia. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 35, Age of Patient: 53, Age of Death: n/a |
| Reference: | Van Goethem et al, 2001; | | Description: | Ocular symptoms, ptosis, Ophthalmoplegia, Muscle weakness, areflexia. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 39, Age of Patient: 39, Age of Death: n/a |
| Reference: | Van Goethem et al, 2001; | | Description: | Ocular symptoms, ptosis, areflexia. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 33, Age of Patient: 33, Age of Death: n/a |
| Reference: | Van Goethem et al, 2001; | | Description: | Ocular symptoms, ptosis, dysphonia, distal sensoral neuropathy, areflexia, pes cavus. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 32, Age of Patient: 32, Age of Death: n/a |
Back to top | Reference: | Van Goethem et al, 2001; | | Description: | Psychiatric symptoms, ptosis, Ophthalmoplegia, Dysphonia, Dysphagia, Muscle weakness, Elevated blood CK, Myogenic EMG, areflexia, distal sensory neuropathy, hearing loss. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 30, Age of Patient: 48, Age of Death: n/a |
| Reference: | Van Goethem et al, 2001; | | Description: | Ptosis, Ophthalmoplegia, Dysphonia, Dysphagia, Muscle weakness, Elevated blood CK, Myogenic EMG, ocular symptoms, areflexia. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 35, Age of Patient: 55, Age of Death: n/a |
| Reference: | Van Goethem et al, 2001; | | Description: | Ptosis, Ophthalmoplegia, Dysphonia, Dysphagia, Muscle weakness, Loss of weight, Elevated blood CK, Myogenic EMG, Distal sensory neuropathy, areflexia, Psychatric symptoms. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 25, Age of Patient: 60, Age of Death: n/a |
| Reference: | Martikainen et al, 2016; | | Description: | Parkinsonism, restless legs syndrome. Good response to levodopa and ropinirole. PEO, cerebellar ataxia, neuropathy, myopathy, sensorineural hearing loss. | | Mutations: | Y955C | | Age group: | adult | | Age of Onset: 40, Age of Patient: 63, Age of Death: n/a |
| Reference: | Pagnamenta et al, 2006; | | Description: | Presented with ptosis and PEO, in early 20’s, premature ovarian failure at 28 years. proximal muscle weakness, exertional dyspnoea and sensory ataxia, Peripheral neuropathy | | Mutations: | Y955C | | SNPs: | Q1236H | | Age group: | adult | | Age of Onset: 22, Age of Patient: 33, Age of Death: n/a |
Back to top | Reference: | Tang et al, 2011; | | Description: | Peripheral neuropathy, myopathy, ptosis, CPEO, COX deficiency, ragged red fibres | | Mutations: | G517V, Y955C | | Age group: | adult | | Age of Onset: n/a, Age of Patient: 47, Age of Death: n/a |
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| Q1236H | | | | Number of patients: (with Q1236H) | 12 | | Found together with: | PNF=Putatively Non-Functional enzyme | | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Horvath et al, 2006; | | Description: | Onset at 2 years with encephalopathy, hepatopathy, and myoclonus achalasia. Diagnosed as Alpers. | | Mutations: | R1096C, R1096C | | SNPs: | Q1236H, Q1236H | | Age group: | infantile | | Age of Onset: 2, 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: | R1096C, R1096C | | SNPs: | Q1236H, Q1236H | | Age group: | infantile | | Age of Onset: 1, Age of Patient: n/a, 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 |
Back to top | 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 |
| Reference: | Zabalza et al, 2014; | | Description: | Unsteady walk, and showed tremor in both legs when standing. Difficulty in concentrating. Dysarthria. No deep tendon reflexes were evident. Sensory axonal neuropathy. Hyperintensities in images of the subcortical frontal and temporal white substances. myoclonia and tonic-clonic seizures. sensory axonal neuropathy in the lower limbs, moderate dysarthria, and an ataxic gait. | | Mutations: | K601E | | SNPs: | D122Y, Q1236H, Y837C | | Age group: | adult | | Age of Onset: 56, Age of Patient: 61, Age of Death: n/a |
| Reference: | Zabalza et al, 2014; | | Description: | ataxia, dysarthria and sensory axonal polyneuropathy. At age 52, the patient developed instability upon walking and paraesthesia in lower limbs, when no other symptoms were apparent. Clinical examination at age 67 revealed dysarthria, gait ataxia, hyporeflexia and tactile hypoestesia. Atrophy of the cerebellar hemispheres. Cognitive decline. left hemiparesis related to a non-traumatic subdural haematoma that required neurosurgical treatment, and began to experience myoclonus and tonic-clonic seizures. weak bilateral palpebral ptosis. | | Mutations: | K601E | | SNPs: | D122Y, Q1236H, Y837C | | Age group: | adult | | Age of Onset: 52, Age of Patient: 67, Age of Death: n/a |
| 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: | Pagnamenta et al, 2006; | | Description: | Presented with ptosis and PEO, in early 20’s, premature ovarian failure at 28 years. proximal muscle weakness, exertional dyspnoea and sensory ataxia, Peripheral neuropathy | | Mutations: | Y955C | | SNPs: | Q1236H | | Age group: | adult | | Age of Onset: 22, Age of Patient: 33, Age of Death: n/a |
Back to top | Reference: | Luoma et al, 2007; | | Description: | Parkinsons disease, tremor, rigidity, hypo-/ bradykinesia. | | Mutations: | | | SNPs: | Q1236H, R722H | | Age group: | adult | | Age of Onset: 66, Age of Patient: 77, Age of Death: n/a |
| Reference: | Luoma et al, 2007; | | Description: | Parkinsons disease, tremor, rigidity, hypo-/ bradykinesia. Ischemic Heart Disease, atrial fibrillation, hypertension | | Mutations: | | | SNPs: | Q1236H, Y831C | | Age group: | adult | | Age of Onset: 70, Age of Patient: 79, Age of Death: n/a |
| Reference: | Wong et al, 2008; | | Description: | Alpers, chorea, microcephaly, leukodystrophy, Seizures, Dementia, developmental delay. | | Mutations: | A467T | | SNPs: | PNF, Q1236H | | Age group: | infantile | | Age of Onset: 1.5, Age of Patient: n/a, 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) Q1236H | PON-P2 predictions results for Q1236H | | Pathogenicity: | Neutral | | Probability: | 0.06 | | Standard Error: | 0.049 | | Prediction result is based on sequence analysis only and may not be accurate. |
Mutation pathogenicity prediction suggests mutation Q1236H is non-pathogenic.
Predicted chance of pathogenicity is 6%. See further details for residue 1236. 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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