Mutation Query
| | | | Allele 1: | G517V | | Allele 2: | R722H | Allelic information known | | Refine query |
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| | | Residue G517 | | Cluster assignment: | | | Cluster description: | Upstream DNA binding channel | | Subcluster: | 2B (residues 496-517) | | Subcluster description: | Subcluster 2B maps to the region of the AID that is predicted to contact the upstream DNA duplex. | | POLG domain: | Spacer domain |
| Residue R722 | | Cluster assignment: | | | Cluster description: | Single Nucleotide Polymorphism | | POLG domain: | Spacer domain |
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Mutation Information
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| G517V | | | | Number of patients: (with G517V) | 12 | | Found as the only mutation: | 67% of entries (8 patients) | | Found together with: | |  | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Burusnukul and de los Reyes, 2009; | | Description: | Global developmental delay, Central hypotonia, Nystagmus and eye surgery, Autistic features, Generalized seizure, Hypnic myoclonia, Intermittent hypoglycemia, Abnormal MRI | | Mutations: | G517V | | Age group: | infantile | | Age of Onset: 0.7, Age of Patient: 4.5, Age of Death: n/a |
| Reference: | Burusnukul and de los Reyes, 2009; | | Description: | Migraines, Complex partial seizure with secondarily generalization, mild developmental delay, muscle cramps and experienced easy fatigability, | | Mutations: | G517V | | Age group: | childhood | | Age of Onset: 7, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Hopkins et al, 2010; | | Description: | diagnosed with type I DM at age 2, diagnosed with adrenal insufficiency and hypothyroidism at age 10, first seizure or dystonic crisis at age 16 years, then neurologic, intensive care unit, and psychiatric admissions for dystonic crises, status epilepticus, nonconvulsive status epilepticus, encephalopathy, depression, suicidal ideation, and psychosis. Elevated lactate, chronic myopathic changes, developmental delay | | Mutations: | G517V | | Age group: | infantile | | Age of Onset: 2, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Hopkins et al, 2010; | | Description: | diagnosed with type I DM at age 5, diagnosed with adrenal insufficiency and hypothyroidism at age 11, presented to neurology at age 17 years, for 2 weeks of headache and recent onset of left facial twitching. neurologic, intensive care unit, and psychiatric admissions for dystonic crises, status epilepticus, nonconvulsive status epilepticus, encephalopathy, depression, suicidal ideation, and psychosis. Elevated lactate, developmental delay | | Mutations: | G517V | | Age group: | childhood | | Age of Onset: 5, Age of Patient: n/a, Age of Death: n/a |
Back to top | Reference: | Woodbridge et al, 2012; | | Description: | neuropathy, dysphagia/ dysarthria, slowly progressive ataxia, hearing loss, slow gastrointestinal transit times, proximal myopathy. Patient #5. | | Mutations: | G517V | | Age group: | juvenile | | Age of Onset: n/a, Age of Patient: 56, Age of Death: n/a |
| Reference: | Staropoli et al, 2012; | | Description: | Diffuse hypotonia, hypoactive reflexes, and roving eye movements. Decreased vis- ual acuity, mild bilateral macular pigmentary changes, normal refractive indices, bilateral ptosis, diffuse cerebral atrophy, and disconjugate, nystagmoid eye movements. In addition to G517V, affected by gene CLN5 c.61C>T, p.Pro21Ser and de novo exon 3 deletion. | | Mutations: | G517V | | Age group: | infantile | | Age of Onset: 0.1, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Schicks et al, 2010; | | Description: | PEO, late-onset ataxia, dysarthria, ptosis, pyramidal tract signs, psychiatric disorders | | Mutations: | G517V | | Age group: | adult | | Age of Onset: 44, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Schicks et al, 2010; | | Description: | early-onset ataxia, dysarthria, pyramidal tract signs, psychiatric disorders, Cerebellar atrophy, Extrapyramidal signs. | | Mutations: | G517V | | Age group: | adult | | Age of Onset: 22, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Wong et al, 2008; | | Description: | Onset at 1 years with microcephaly, developmental delay/ dementia, and liver dysfunction. Authors reported as undiagnosed. | | Mutations: | G517V, R1128H | | Age group: | infantile | | Age of Onset: 1, Age of Patient: n/a, Age of Death: n/a |
Back to top | Reference: | Wong et al, 2008; | | Description: | Onset at 1 years with myopathy, developmental delay/ dementia, RRF, and elevated CK. Authors reported as undiagnosed. | | Mutations: | D1196N, G517V | | Age group: | infantile | | Age of Onset: 1, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Bolszak et al, 2009; | | Description: | Onset at 4 months with generalized tonic-clonic seizure, evolved to status epilepticus, treated with valproate, Progressive encephalopathy, and psychomotor development deficient by age 2, mentally retarded, ataxic and hyperkinetic. At the last follow-up visit at age 17 years, he was severely retarded, autistic, and ataxic. During 12 months of valproate treatment serum alanine aminotransferase (ALAT) increased from 29 to 71 U/L (normal < 40 U/L), and after discontinuation of the medication, ALAT values varied between 5 and 12 U/L. | | Mutations: | G517V | | SNPs: | R722H | | Age group: | infantile | | Age of Onset: 0.33, Age of Patient: 17, Age of Death: n/a |
| 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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| R722H | | | | Number of patients: (with R722H) | 17 | | Found as the only mutation: | 59% of entries (10 patients) | | Found together with: | | | Show Patient Data |
| Patient data are sorted by mutation combination frequency. | Reference: | Luoma et al, 2007; | | Description: | Parkinsons disease, tremor, rigidity, hypo-/ bradykinesia. Hypertension | | Mutations: | | | SNPs: | R722H | | Age group: | adult | | Age of Onset: 57, Age of Patient: 67, Age of Death: n/a |
| Reference: | Komulainen et al, 2010; | | Description: | Cataract, balance disturbances, retinal rupture, tinnitus, unilateral deafness | | Mutations: | | | SNPs: | R722H | | Age group: | adult | | Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Komulainen et al, 2010; | | Description: | Coronary heart disease, delayed puberty, sensorineural hearing loss | | Mutations: | | | SNPs: | R722H | | Age group: | adult | | Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Komulainen et al, 2010; | | Description: | Delayed puberty, hypogonadism, transient vertigo, visual field defect | | Mutations: | | | SNPs: | R722H | | Age group: | adult | | Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a |
Back to top | Reference: | Komulainen et al, 2010; | | Description: | Diabetes mellitus, hypothyreosis, cerebral infarction, hypertension, hypercholesterolemia, learning difficulties | | Mutations: | | | SNPs: | R722H | | Age group: | adult | | Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Komulainen et al, 2010; | | Description: | Hypothyreosis, gestational diabetes mellitus | | Mutations: | | | SNPs: | R722H | | Age group: | adult | | Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Komulainen et al, 2010; | | Description: | Mental retardation | | Mutations: | | | SNPs: | R722H | | Age group: | adult | | Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Komulainen et al, 2010; | | Description: | Premature puberty, short stature, fertility problems, gestational diabetes mellitus | | Mutations: | | | SNPs: | R722H | | Age group: | juvenile | | Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Komulainen et al, 2010; | | Description: | Tinnitus, benign cardiac arrhythmias | | Mutations: | | | SNPs: | R722H | | Age group: | adult | | Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a |
Back to top | Reference: | Komulainen et al, 2010; | | Description: | Transient hypertension, benign cardiac arrhythmias, fertility problems | | Mutations: | | | SNPs: | R722H | | Age group: | adult | | Age of Onset: n/a, Age of Patient: n/a, Age of Death: n/a |
| Reference: | Komulainen et al, 2010; | | Description: | Mild dementia, sensorineural hearing impairment, diabetes mellitus, osteoarthritis, hypertension, coronary heart disease, areflexia due to diabetic neuropathy. She had a mild left motor hemiparesis at the age of 74 years due to a lacunar brain infarct. Patient A3. Elder sister of patient A1. | | Mutations: | | | SNPs: | R722H, R722H | | Age group: | adult | | Age of Onset: 74, Age of Patient: 86, Age of Death: n/a |
| Reference: | Komulainen et al, 2010; | | Description: | Moderate dementia, sensorineural hearing impairment, occasional headaches, bilateral cataract, chronic gastritis. Occasional headaches started at 30 years old. Patient A2. Younger sister of patient A1. | | Mutations: | | | SNPs: | R722H, R722H | | Age group: | adult | | Age of Onset: 30, Age of Patient: 78, Age of Death: n/a |
| Reference: | Komulainen et al, 2010; | | Description: | Severe dementia, sensorineural hearing impairment, diabetes mellitus, PEO, dysphagia, neuropathic pain in the legs, multiple mtDNA deletions in muscle. Clear age of onset not reported, hearing aid at 72 years. Patient A1. | | Mutations: | | | SNPs: | R722H, R722H | | Age group: | adult | | Age of Onset: 72, Age of Patient: 83, 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 |
Back to top | Reference: | Bolszak et al, 2009; | | Description: | Onset at 4 months with generalized tonic-clonic seizure, evolved to status epilepticus, treated with valproate, Progressive encephalopathy, and psychomotor development deficient by age 2, mentally retarded, ataxic and hyperkinetic. At the last follow-up visit at age 17 years, he was severely retarded, autistic, and ataxic. During 12 months of valproate treatment serum alanine aminotransferase (ALAT) increased from 29 to 71 U/L (normal < 40 U/L), and after discontinuation of the medication, ALAT values varied between 5 and 12 U/L. | | Mutations: | G517V | | SNPs: | R722H | | Age group: | infantile | | Age of Onset: 0.33, Age of Patient: 17, Age of Death: n/a |
| 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. | | Mutations: | | | SNPs: | Q1236H, R722H | | Age group: | adult | | Age of Onset: 66, Age of Patient: 77, Age of Death: n/a |
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The following information is based on PON-P2 mutation pathogenicity prediction software results. Cluster 2 mutation with a non-cluster-mapping mutation (SNP) R722H | PON-P2 predictions results for R722H | | Pathogenicity: | Neutral | | Probability: | 0.057 | | Standard Error: | 0.022 | | Prediction result is based on sequence analysis only and may not be accurate. |
Mutation pathogenicity prediction suggests mutation R722H is non-pathogenic.
Predicted chance of pathogenicity is 5.7%. See further details for residue 722. 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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