Table 1.
Mutations identified in the POLG2 gene in mitochondrial disease patients
| Patient | Agea | Gender | cDNA mutation | Amino acid change | Reference and Symptoms |
|---|---|---|---|---|---|
| 1b | 8 years | F | c.307G>A | p.G103S | This study. No symptoms available |
| 2 | 11 years | M | c.457C>G | p.L153V | This study. Headaches/migraines, Peripheral neuropathy, Exercise intolerance/easy fatigue, muscle weakness/DMD-like, easy fatigability, gastrointestinal reflux, delayed gastric emptying |
| 3 | 0.5 year | M | c.614C>G | p.P205R | This study. Irritable, failure to thrive, lethargy, central hypotonia, liver disease, refractory seizures |
| 4 | 19 years | F | c.1105A>G | p.R369G | This study. Exercise intolerance/easy fatigue, muscle weakness/DMD-like, cramps after exercise, easy fatigability, ophthalmoparesis, CPEO, abnormal EMG/NCV, ptosis, gastrointestinal reflux, delayed gastric emptying, apnea/hypoventilation, respiratory deficiency/failure, lactic acidosis, CPK abnormalities, failure to thrive, abnormal histology, abnormal ultrastructure (EM) mitochondria |
| 5 | 11 years | F | c.1158T>G | p.D386E | This study. Developmental delay, dementia/encephalopathy, ataxia, seizures, refractory/intractable seizure, muscle weakness/DMD-like, constipation, high CSF protein, short stature, failure to thrive, microcephaly, abnormal EEG, cerebellar atrophy, abnormal MRI |
| 6 | 1 year | M | c.1158T>G | p.D386E | This study. Hypotonia/floppy baby, hepatic failure, ketosis, lactic acidosis, alopecia |
| 7 | 9 years | M | c.1268C>A | p.S423Y | This study. Developmental delay, hypotonia/floppy baby, seizures, spasticity, gastrointestinal reflux, respiratory deficiency/failure |
| 8c | 2 years | F | c.1247G>C | p.G416A | This study and reference (34). Developmental delay, hypotonia/floppy baby, short stature, dysmorphic features, MRS/lactate peak, abnormal MRI, alopecia. No biochemical defect found and previously published as a possible SNP |
| 9d | 60 years | F | c.1352G>A | p.G451E | Reference (12). adPEO, ptosis, exercise intolerance, muscle pain, mild weakness of facial and limb muscles, impaired glucose intolerance |
| 10 | 8 years | M | c.1423_1424delTT | p.L475DfsX2 | This study. Developmental delay, hypotonia/floppy baby, seizures, constipation, elevated transaminases, ketosis, high CSF protein, abnormal EEG, cerebellar atrophy, abnormal MRI, cortical blindness |
| 11e | 62 years | F | c.1207_1208ins24; c. 505G>A; c.1110+44T>C; c.1191+7_1191+8insT | p.deltaV398-K431 and p.A169T | Reference (27). Bilateral ptosis at 30 years, exercise intolerance, muscle weakness, mild creatine kinase increase and multiple mtDNA deletions |
All mutations were found as heterozygous changes.
aAge at molecular diagnosis.
bSequence determined from a control subject in this study not diagnosed with POLG-related mitochondrial disease.
cPreviously published mutation in POLG2 found in one subject in this study.
dPreviously published mutation in POLG2 not found in this study.
ePreviously published mutations not found in this study with the predicted protein sequence pdeltaV398-K431 based on the observation that POLG2 exon 7 was skipped in cDNA analysis (27). It is unknown whether or not the patient is a complex heterozygote (all mutations on one allele) or whether she is a compound heterozygote (different mutations on different alleles); however, only one of her three unaffected brothers also carried all four mutations suggestive of a complex heterozygote.