Table 3.
Phenotypes Associated with a Single POLG Variant
| Nucleotide Change | Amino Acid Change | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No. | Gender | Onset (yrs) | DD or Dementia | Sz | Liver | PEO | Lact | Dx | Other Symptoms | Allele 1 | Allele 2 | Allele 1 | Allele 2 | Domains |
| 34 | M | 1 | + | + | + | - | + | ?Alpers | - | c.915C>G | - | p.S305R | - | Exo |
| 35 | M | 66 | - | - | - | + | - | adPEO | Hearing loss, ptosis | c.3235A>C | - | p.I1079L | P | |
| 36 | F | 46 | - | - | - | + | - | adPEO | Ptosis, hearing loss, muscle weakness, optic atrophy | c.3285C>G | - | p.S1095R | P | |
| 37 | F | 25 | - | - | - | + | + | adPEO | Ptosis, exercise intolerance, fatigue, ragged red fibers | c.2740A>C | - | p.T914P | P | |
| 38 | F | 16 | + | + | - | - | - | U | Short-stature, Leigh-like disease, neuropathy, stroke, dystonia, chorea, diabetes, myoclonus | c.1550G>T | - | p.G517V | L | |
| 39 | M | 2 | + | + | - | - | - | U | Half-sib with similar symptoms | c.1550G>T | - | p.G517V | L | |
| 40 | F | 2.5 | + | + | + | - | + | U | Chorea, myopathy, Leigh-like disease | c.1550G>T | - | p.G517V | L | |
| 41 | F | 6 | + | - | - | - | + | U | Sideroblastic anemia, splenomegaly | c.1550G>T | - | p.G517V | L | |
| 42 | M | 13 | + | - | - | + | - | U | Pearson syndrome to KSS | c.1550G>T | - | p.G517V | L | |
| 43 | F | 0.1 | NA | NA | NA | NA | NA | U | - | c.2492A>G | - | p.Y831C | P | |
| 44 | M | 0.1 | + | + | - | - | - | U | Hypotonia | c.2492A>G | - | p.Y831C | P | |
| 45 | M | 1.8 | - | - | - | - | + | U | Autism, hypotonia | c.2492A>G | - | p.Y831C | P | |
| 46 | F | 9 | + | + | - | - | - | U | - | c.2492A>G | - | p.Y831C | P | |
| 47 | F | 14 | NA | NA | NA | NA | NA | U | - | c.2492A>G | - | p.Y831C | P | |
| 48 | M | 19 | + | - | - | + | - | U | Neuropathy, ataxia, hearing loss, short stature, muscle weakness, fatigue | c.2492A>G | - | p.Y831C | P | |
| 49 | F | 5 | + | + | - | - | - | U | Failure to thrive | c.32G>A | - | p.G11D | MTS | |
| 50 | F | 3 | - | - | + | - | - | U | Hypotonia, failure to thrive, short stature, respiratory failure | c.328C>T | - | p.H110Y | Exo | |
| 51 | M | 0.5 | NA | NA | NA | NA | NA | U | NA | c.752C>T-c.1760C>T | - | p.T251I-p.P587L | Exo/L | |
| 52 | M | 4 | - | + | - | + | - | U | Neuropathy, ataxia, ptosis | c.752C>T-c.1760C>T | - | p.T251I-p.P587L | Exo/L | |
| 53 | M | 13 | + | - | + | - | - | U | Muscle weakness, optic atrophy | c.1174C>G | - | p.L392V | Exo | |
| 54 | F | 39 | - | - | - | - | + | U | Muscle weakness, exercise intolerance, hearing loss, arhytthmia | c.1849C>T | - | p.R617C | L | |
| 55 | M | 2 | + | - | - | - | - | U | - | c.2209G>C | - | p.G737R | L | |
| 56 | F | 3 | + | + | - | - | + | U | - | c.2209G>C | - | p.G737R | L | |
| 57 | M | 30 | NA | NA | NA | NA | U | - | c.2209G>C | - | p.G737R | L | ||
| 58 | M | 9 | - | - | - | + | - | U | Muscle weakness | c.2564T>C | - | p.V855A | P | |
| 59 | M | 2 | - | + | - | - | - | U | Ataxia, hypotonia | c.2590C>T | - | p.R964C | P | |
| 60 | F | 0.1 | + | - | + | - | + | U | Hearing loss, failure to thrive, Generalized ETC complex deficiency | c.2864A>G | - | p.Y955C | P | |
| 61 | F | 0.8 | + | + | - | - | - | U | Retinitis pigmentosa, hearing loss, failure to thrive | c.3614G>C | - | p.G1205 A | P | |
Nucleotide numbering reflects cDNA numbering with +1 corresponding to the A of the ATG translation initiation codon in the reference sequence NM_002693.1, according to journal guidelines (www.hgvs.org/mutnomen). The initiation codon is codon 1. Novel mutations are shown in bold and neutral variants are in shown in blue.
Abbreviations: adPEO = autosomal dominant Progressive External Ophthalmoplegia, U=unclassified Exo = exonuclease domain; L = linker region; P = Polymerase domain. DD = Developmental Delay; Sz = Seizures; Lact = Elevated lactate; Dx = Diagnosis