Mutation Query
| | | | Allele 1: | H1134R | | Allele 2: | Y831C | Allelic information known | | Refine query |
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| | | Residue Y831 | | Cluster assignment: | | | Cluster description: | Single Nucleotide Polymorphism | | POLG domain: | Polymerase domain |
| Residue H1134 | | Cluster assignment: | | | Cluster description: | Polymerase active site and environs | | Subcluster: | 1F (residues 1098-1138) | | Subcluster description: | This subcluster forms a segment of the pol active site and contains two highly conserved motifs that are found in all family A polymerases, the Pol C motif and motif 6 (Loh and Loeb, 2005). | | POLG domain: | Polymerase domain |
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Mutation Information
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| H1134R | | | | Number of patients: (with H1134R) | 1 | | Non-allelic with: | Y831C (100%) |  | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Taanman et al, 2009; | | Description: | Anorexia, FTT, drowsiness, hepatomegaly, peripheral odema, liver failure. Onset at 3 months with infantile hepatocerebral mtDNA depletion. Death at 6 months. Asymptomatic mother and father. | | Mutations: | H1134R | | SNPs: | Y831C | | Age group: | infantile | | Age of Onset: 0.3, Age of Patient: n/a, Age of Death: 0.5 |
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| Y831C | | | | Number of patients: (with Y831C) | 7 | | Found as the only mutation: | 57% of entries (4 patients) | | Found together with: | | | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Mancuso et al, 2004b; | | Description: | Presented with progressive bilateral ptosis, diplopia, muscle weakness, and exercise intolerance at 28 years of age. Ophthalmoplegia and severe bilateral ptosis developed by age 44, sensory neuropathy at age 45, and at age 47 she developed slowly progressive resting hand tremor, slowing of her gait, bradykinesia, rigidity, and slurred speech. Muscle biopsy showed numerous ragged-red fibers and Southern blot analysis showed multiple deletions of mtDNA. insipient parkinsonism. | | Mutations: | | | SNPs: | Y831C | | Age group: | adult | | Age of Onset: 28, Age of Patient: 49, Age of Death: n/a |
| Reference: | Woodbridge et al, 2012; | | Description: | CPEO, Seizures, neuropathy, ataxia, hepatopathy, dysphagia/ dysarthria, gastric and small bowel dysmotility after a colectomy, and multiple admissions for recurrent pseudo-obstruction, proximal myopathy, | | Mutations: | | | SNPs: | Y831C | | Age group: | juvenile | | Age of Onset: n/a, Age of Patient: 34, Age of Death: n/a |
| Reference: | Woodbridge et al, 2012; | | Description: | Seizures, liver function tests change, migraine, increasing proximal weakness and myalgia, mild asymmetrical ptosis | | Mutations: | | | SNPs: | Y831C | | Age group: | adult | | Age of Onset: n/a, Age of Patient: 46, Age of Death: n/a |
| Reference: | Barthelemy et al, 2002; | | Description: | severe mitochondrial DNA depletion in muscle and kidney. Patient also has heteroplasmic mtDNA alterations including large-size deletions and point mutations in the D-loop region. Severe sensorineural deafness, intolerance to exercise and nephrotic syndrome. Retinitis pigmentosa, optic atrophy, ophthalmoplegia, epilepsy, mental deterioration and permanent muscle weakness with diffuse myalgia and respiratory distress. | | Mutations: | | | SNPs: | Y831C | | Age group: | childhood | | Age of Onset: 6, Age of Patient: n/a, Age of Death: 13 |
Back to top | Reference: | Taanman et al, 2009; | | Description: | Anorexia, FTT, drowsiness, hepatomegaly, peripheral odema, liver failure. Onset at 3 months with infantile hepatocerebral mtDNA depletion. Death at 6 months. Asymptomatic mother and father. | | Mutations: | H1134R | | SNPs: | Y831C | | Age group: | infantile | | Age of Onset: 0.3, Age of Patient: n/a, Age of Death: 0.5 |
| Reference: | Ylönen et al, 2013; | | Description: | late onset parkinsons. Tremor. Hyperreflexia. | | Mutations: | | | SNPs: | R722H, Y831C | | Age group: | adult | | Age of Onset: 56, Age of Patient: n/a, 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 |
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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) Y831C Mutation pathogenicity prediction for mutation Y831C is unreliable. Mutation Y831C is outside of assigned pathogenic clusters, and therefore risk that it contributes to a POLG-related syndrome is low. See further details for residue 831. 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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