Table 1.
Mutations and Clinical Features of Pol III-Related Leukodystrophies
| Individual Number | Family Number | Ethnicity | Diagnosis |
Mutation(s) |
Gender | Age of Onset (Years) | Developmental Delay | Cognitive Regression | Seizures | Optic Atrophy | Gaze-Evoked Nystagmus | Abnormal Smooth Pursuits | Vertical Gaze Limitation | Dysphagia | Hypersalivation | Upper motor Neuron Signs | Tremor | Cerebellar Signs | Wheelchair | Age of Wheelchair Use (Years) | Hypodontia | Hypogonadotropic Hypogonadism | Nerve Biopsy | Age of Death | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| DNA | Protein | ||||||||||||||||||||||||
| 1 | I | FC | TACH | c.1674C>G | p.Phe558Leu | M | 2 | + | + | − − |
− | + | + | − | − | − | + | + | + | + | 5 | − | − | N/A | − |
| c.3742insACC | p.1248insThr | ||||||||||||||||||||||||
| 2 | II | FC | TACH | c.2015G>A | p.Gly672Glu | M | 1 | + | + | + | + | + | + | + | + | + | + | + | + | + | 8 | + | − | N/A | − |
| 3 | II | FC | TACH | c.2015G>A | p.Gly672Glu | M | 5 | + | + | − | − | − | + | − | − | − | + | + | + | − | − | + | − | N/A | − |
| 4 | II | FC | TACH | c.2015G>Aa | p.Gly672Glua | F | 3 | − | + | − | + | − | + | − | + | + | + | + | + | + | 8 | − | − | − | 21 |
| 5 | III | FC | TACH | c.2015G>A | p.Gly672Glu | M | 3 | − | + | − | + | + | + | + | + | + | + | + | + | + | 12 | − | + | − | − |
| 6 | IV | FC | TACH | c.2015G>A | p.Gly672Glu | F | 5 | − | + | − | + | − | + | − | − | + | + | + | + | − | − | − | + | N/A | − |
| 7 | V | W USA | 4H | c.2554A>G | p.Met852Val | F | 13 | − | + | ± | − | − | + | + | + | + | + | − | + | + | 24 | + | + | + | − |
| c.2711-1G>A | p.Arg873AlafsX878 | ||||||||||||||||||||||||
| 8 | VI | AA USA | 4H | c.2324A>T | p.Asn775Ile | F | 0 | + | + | − | − | − | + | + | + | + | + | − | + | + | 10 | + | + | N/A | − |
| c.1114G>A | p.Asp372Asn | ||||||||||||||||||||||||
| 9 | VII | W USA | 4H | c.2830G>T | p.Glu944X | M | 13 | − | + | ± | − | − | + | + | + | − | + | − | + | + | 30 | + | + | + | 36 |
| c.3013C>T | p.Arg1005Cys | ||||||||||||||||||||||||
| 10 | VIII | W USA | 4H | c.2554A>G | p.Met852Val | F | 12 | − | + | − | − | − | + | + | + | − | + | − | + | + | 24 | + | + | + | − |
| c.2711-1G>A | p.Arg873AlafsX878 | ||||||||||||||||||||||||
| 11 | IX | France | 4H | c.4006C>T | p.Gln1336X | F | 1 | + | + | − | − | − | + | − | − | − | + | + | + | − | − | + | + | N/A | − |
| c.1907C>A | p.Ser636Tyr | ||||||||||||||||||||||||
| 12 | X | Syria | LO | c.2003+18G>A | p.Tyr637CysfsX650 | M | 13 | − | + | − | − | − | − | − | − | − | + | − | + | + | 23 | + | − | N/A | 28 |
| 13 | X | Syria | LO | c.2003+18G>A | p.Tyr637CysfsX650 | F | 12 | − | + | − | − | − | − | − | − | − | + | + | + | + | 20 | + | − | N/A | − |
| 14 | X | Syria | LO | c.2003+18G>A | p.Tyr637CysfsX650 | F | 11 | − | + | − | − | − | − | − | − | − | + | + | + | + | 20 | + | − | N/A | − |
| 15 | X | Syria | LO | c.2003+18G>A | p.Tyr637CysfsX650 | F | 11 | − | + | − | − | − | − | − | − | − | + | − | + | − | − | + | − | N/A | − |
| 16 | X | Syria | LO | c.2003+18G>A | p.Tyr637CysfsX650 | M | 12 | − | + | − | − | − | − | − | − | − | + | − | + | − | − | + | − | N/A | − |
| 17 | X | Syria | LO | c.2003+18G>A | p.Tyr637CysfsX650 | M | 12 | − | + | − | − | − | − | − | − | − | + | − | + | − | − | + | − | N/A | − |
| 18 | XI | W Europe | LO | c.418C>T | p.Arg140X | F | 3 | + | + | − | − | − | + | − | − | − | + | + | + | − | − | + | − | − | − |
| c.2554A>G | p.Met852Val | ||||||||||||||||||||||||
| 19 | XII | Guatemala | LO | c.2171G>A | p.Cys724Tyr | M | 2 | + | + | − | − | − | + | + | − | + | + | + | + | + | 9 | + | N/A | N/A | − |
POLR3A mutations and clinical features of individuals with TACH, 4H, and LO. A total of 14 different mutations were found: missense, nonsense, insertion, and splice-site mutations. Individuals 1-53 and 610 with TACH, individuals 7-108 with 4H and individuals 12-174,5 with LO have been published previously. The following abbreviations are used: +, positive or present; −, negative or absent; FC, French-Canadian; AA USA, African American from USA; W Europe, white from Europe; W USA, white from USA; F, female; M, male; and N/A, not available.
a
Presumed mutation the deceased individual 4 for which DNA was not available.