POLG Pathogenicity Prediction Server

Mutation Information

Patient data are sorted by mutation combination frequency.

Reference:

Horvath et al, 2006;

[PubMed]

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;

[PubMed]

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;

[PubMed]

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;

[PubMed]

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

Reference:

Luoma et al, 2005;

[PubMed]

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;

[PubMed]

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;

[PubMed]

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;

[PubMed]

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;

[PubMed]

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

Reference:

Luoma et al, 2007;

[PubMed]

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;

[PubMed]

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;

[PubMed]

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

Patient data are sorted by mutation combination frequency.

Reference:

Luoma et al, 2007;

[PubMed]

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;

[PubMed]

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;

[PubMed]

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;

[PubMed]

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

Reference:

Komulainen et al, 2010;

[PubMed]

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;

[PubMed]

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;

[PubMed]

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;

[PubMed]

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;

[PubMed]

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

Reference:

Komulainen et al, 2010;

[PubMed]

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;

[PubMed]

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;

[PubMed]

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;

[PubMed]

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;

[PubMed]

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:

Bolszak et al, 2009;

[PubMed]

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:

YlÃ¶nen et al, 2013;

[PubMed]

Description:

late onset parkinsons. Tremor. Hyperreflexia.