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:

Horvath et al, 2006;

[PubMed]

Description:

Onset at 7 years with encephalopathy, hepatopathy, and SLE seizures. Diagnosed as alpers. Death at 8 years.

Mutations:

R1096H, R627Q

Age group:

childhood

Age of Onset: 7, Age of Patient: n/a, Age of Death: 8

Reference:

Schulte et al, 2009;

[PubMed]

Description:

At 43 years of age, cerebellar ataxia, dysarthria/dysphagia, sensory neuropathy, PEO, distal muscle wasting, mild cerebellar atrophy.

Mutations:

R1096H, R627Q

Age group:

adult

Age of Onset: 25, Age of Patient: 43, Age of Death: n/a

Reference:

Schicks et al, 2010;

[PubMed]

Description:

early-onset ataxia, PEO, dysarthria, ptosis, sensory neuropathy, hypoacusis, cerebellar athropy.

Mutations:

R1096H, R627Q

Age group:

adult

Age of Onset: 22, Age of Patient: n/a, Age of Death: n/a

Reference:

Tang et al, 2011;

[PubMed]

Description:

Dementia/encephalopathy, infantile spasms, cerebral artery occlusion, headache/migraine, stroke, constipation. 74% mtDNA copy number in blood.

Mutations:

R627Q, R852C

SNPs:

G11D

Age group:

juvenile

Age of Onset: n/a, Age of Patient: 25, Age of Death: n/a

Reference:

Wong et al, 2008;

[PubMed]

Description:

Ataxia Neuropathy Spectrum, Seizures, PEO, lactic acidosis, stroke, chorea, ataxia, ptosis, retinitis pigmentosa, liver transplans

Mutations:

R627Q, R852C

SNPs:

G11D

Age group:

juvenile

Age of Onset: 15, Age of Patient: n/a, Age of Death: n/a

Reference:

Wong et al, 2008;

[PubMed]

Description:

Seizures, PEO, Ataxia Neuropathy Spectrum, Stroke, chorea, ataxia, ptosis, retinitis pigmentosa, liver transplant

Mutations:

R627Q, R852C

SNPs:

G11D

Age group:

juvenile

Age of Onset: 15, Age of Patient: 19, Age of Death: n/a

Reference:

Luoma et al, 2005;

[PubMed]

Description:

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:

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:

Deschauer et al, 2007;

[PubMed]

Description:

vomiting, headache, sensory ataxia, areflexia, focal seizures, status epilepticus. MELAS.

Mutations:

G848S, R627Q

Age group:

adult

Age of Onset: 21, Age of Patient: n/a, Age of Death: n/a

Reference:

Schulte et al, 2009;

[PubMed]

Description:

At 35 years of age, dysarthria/dysphagia, sensory neuropathy, PEO, distal muscle wasting, phobia anxiety disorder, mild cerebellar atrophy (MRI)

Mutations:

G848S, R627Q

Age group:

adult

Age of Onset: 29, Age of Patient: 35, Age of Death: n/a

Reference:

Hanisch et al, 2014;

[PubMed]

Description:

Ataxia, ptosis, myalgia, sensory neuropathy, motor neuropathy, axonal neuropathy, demyelinating neuropathy.

Mutations:

A467T, R627Q

Age group:

adult

Age of Onset: 46, Age of Patient: 50, Age of Death: n/a

Reference:

Baruffini et al, 2011;

[PubMed]

Description:

generalized seizures and myoclonic jerks at age 5, ataxia and sensory-axonal peripheral neuropathy onset in teen years.

Mutations:

R627Q, S305R

Age group:

childhood

Age of Onset: 5, Age of Patient: 25, Age of Death: n/a

Reference:

Horvath et al, 2006;

[PubMed]

Description:

Onset at 0.5 years with encephalopathy and hepatopathy. Diagnosed as alpers. Death at 1.3 years

Mutations:

R309H, R627Q

Age group:

infantile

Age of Onset: 0.5, Age of Patient: n/a, Age of Death: 1.3

Database patient data suggest that Q1236H is a known SNP.This mutation is unlikely to cause a POLG-related syndrome.

See full list of known POLG SNPs.

Database patient data is inconclusive about the dominant status of mutation R627Q.

See full list of putatively-dominant POLG mutations

Example input: A467T T914P

Example input: A467T, T914P

Mutations in the same allele can be separated with a comma

Separate mutations by commas

Mutations outside assigned pathogenic clusters are considered to be SNPs (single nucleotide polymorphisms).