Mutation Query
| | | | Allele 1: | P648R | | Allele 2: | P648R | Allelic information known | | Refine query |
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| | | 648 |  |  |
| | Residue P648 | | Cluster assignment: | | | Cluster description: | Putative protein-protein interactions | | Subcluster: | 5A (residues 623-648) | | Subcluster description: | Located in the periphery of the IP subdomain of the spacer domain, distant from the DNA binding channel | | POLG domain: | Spacer domain |
| Residue P648 | | Cluster assignment: | | | Cluster description: | Putative protein-protein interactions | | Subcluster: | 5A (residues 623-648) | | 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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| P648R | | | | Number of patients: (with P648R) | 7 | | Found together with: | PNF=Putatively Non-Functional enzyme |  | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Ferreira et al, 2011; | | Description: | Onset at 39 years with SANDO. | | Mutations: | P648R, R807C | | Age group: | adult | | Age of Onset: 39, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Gago et al, 2006; | | Description: | Man presented at age 39 progressive bilateral ptosis, unsteadiness gait and muscle weakness with difficulty in dressing and lifting objects. Three years later he noticed dysphagia and diplopia and sought medical advice. Neurological examination revealed droopy eyes which worsened after repeated eye movements and external ophthalmoparesis with diplopia on horizontal gaze. The patient also presented fluctuant dysarthria and dysphagia which worsened at the end of the day. There was distal limb muscles weakness with reduced deep tendon reflexes. Perception of vibration and position was absent below the iliac crests. Touch, pain and temperature senses were preserved. Signs of cerebellar dysfunction were also evident. Romberg sign was positive. multiple mtDNA deletions in muscle Summary: Sensory ataxia with neuropathy, dysarthria and ophthalmoparesis represent the clinical triad of SANDO | | Mutations: | P648R, R807C | | Age group: | adult | | Age of Onset: 39, Age of Patient: n/a, Age of Death: 44 |
| Reference: | Miguel et al, 2014; | | Description: | progressive bilateral ptosis, unsteadiness gait and muscles weakness at the age of 39 and developed dysphagia and diplopia 3 years later. bilateral blepharoptosis, external ophthalmoparesis with diplopia on horizontal gaze, dysarthria and dysphagia at 44. distal limb muscles weakness, with depressed deep tendon reflexes, and impaired proprioception and vibration sense. Positive Romberg sign. axonal sensory polyneuropath, SANDO. parkinsonism, with hand rest tremor, moderate limb bradykinesia, cogwheel rigidity and hypomimic face. Multiple mtDNA deletions were detected. | | Mutations: | P648R, R807C | | Age group: | adult | | Age of Onset: 39, Age of Patient: 52, Age of Death: n/a |
| Reference: | Ferreira et al, 2011; | | Description: | Ptosis, oculopharyngeal muscular dystrophy-like, pigmentary retinopathy. | | Mutations: | P587L, P648R | | SNPs: | T251I | | Age group: | adult | | Age of Onset: 59, Age of Patient: 67, Age of Death: n/a |
Back to top | Reference: | Horvath et al, 2006; | | Description: | Onset at 25 years with PEO, ataxia, dysphagia, myopathy, and thyroid disease. | | Mutations: | P648R, P648R | | Age group: | adult | | Age of Onset: 25, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Horvath et al, 2006; | | Description: | Onset at 53 years with PEO, neuropathy. | | Mutations: | P648R, R1096C | | Age group: | adult | | Age of Onset: 53, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Ferreira et al, 2011; | | Description: | Parkinsons. Slowly progressive bilateral blepharoptosis, external ophthalmoplegia, dysphagia and dysarthria, presented with right-dominant parkinsonian features at age 56, comprising hand and lower limb rest tremor, mild upper limb cogwheel rigidity, right foot dystonic movements, hypomimic face and postural instability. impairment of vibration and pinprick sensations in glove-stocking distribution and absence of lower limb tendon reflexes. decline in attention and visuospatial functions. Axonal sensory polyneuropathy. ragged red fibers, multiple mtDNA deletions, | | Mutations: | P648R, PNF | | Age group: | adult | | Age of Onset: 56, Age of Patient: 64, 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 5 and 5: Age of onset information is extracted from a total of 70 patients and/ or patient families. | Age of onset | | |
70- 35- | 1
| 13
| 24
| 32
| | | infantile | childhd | juvenile | adult | | | 1% | 19% | 34% | 46% | |
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 cluster5-cluster5 mutations | |
| Symptoms in patients with combination
cluster5:cluster5 | | Movement disorder (ataxia) | 87.1% | | Epilepsy | 47.1% | | PEO | 38.6% | | Dysarthria | 35.7% | | Nystagmus | 31.4% | | Myoclonic seizures | 24.3% | | Headache/ migraine | 21.4% | | Polyneuropathy | 20.0% | | Status epilepticus | 18.6% | | Stroke | 17.1% | | Ophthalmoplegia | 15.7% | | Dysphagia | 15.7% | | Peripheral neuropathy | 14.3% | | Ptosis | 14.3% | | External ophthalmoplegia | 14.3% | | Tremor | 12.9% | | Liver failure | 8.6% | | Diplopia | 7.1% | | Stroke-like episodes | 7.1% | | Hearing loss | 7.1% | | Cerebellar atrophy | 5.7% | | +22 other symptoms in under 5.0% of the patients |
| | Data gathered from clinical descriptions for 70 patients |
| Symptoms by group | | Ataxia | 88.6% | | CNS symptoms | 74.3% | | Seizures | 60.0% | | CPEO | 52.9% | | Neuropathy | 35.7% | | Migraines | 21.4% | | Other | 18.6% | | Hepatopathy | 14.3% | | Myopathy | 8.6% | | GI symptoms | 2.9% | | Alpers syndrome | 1.4% | | Developmental Delay | 1.4% | | Unknown | 1.4% |
| | [Show grouping information] |
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