Table 1 Summary of molecular and key clinical findings.
F1 IV:1/ F11 V:1/V:2/ V:3/V:4 | F2 IV:3 | F3 II:2 | F4 V:3/V:4 | F5 II:1 | F6 IV:1 | F7 IV:1/IV:4/F8 IV:1 /IV:2/F13 II:2 | F9 II:1/ F10 II:4/ F15 II:1 | F9 II:1/F15 II:1 | F10 II:4 | F12 II:1 | F14 II:2 | F16 II:1 | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Molecular genetics summary | ||||||||||||||
Chr16 g. position | g.75674175A>G | g.75669866G>C | g.75668181C>G | g.75668081A>G | g.75665680G>A | g.75665629T>C | g.75662474T>A | g.75669880G>A | g.75669683T>A | g.75662504C>T | g.75663371G>A | g.75668082G>A | g.75665702G>A | g.75662486G>A |
KARS1 c. position | c.379T>C | c.697C>G | c.889C>G | c.989T>C | c.1073C>T | c.1124A>G | c.1772A>T | c.683C>T | c.774A>T | c.1742G>A | c.1577C>T | c.988C>T | c.1051C>T | c.1760C>T |
KARS1 p. position | F127L | L233V | P297A | L330P | T358M | Y375C | N591I | P228L | R258S | R581Q | A526V | L330F | R351W | T587M |
phyloP | 8.92 | 5.66 | 9.87 | 9.34 | 9.84 | 8.02 | 7.95 | 9.59 | 0.18 | 7.77 | 5.94 | 5.86 | 2.14 | 6.10 |
CADD | 29.7 | 22.2 | 27.0 | 31 | 29.4 | 32 | 28.1 | 25.5 | 25.2 | 28.6 | 31 | 29.4 | 32 | 32 |
MT | DC | DC | DC | DC | DC | DC | DC | DC | DC | DC | DC | DC | DC | DC |
PP2 | PrD | B | PrD | PrD | PrD | PrD | PrD | PrD | PrD | PrD | PrD | PrD | PrD | PrD |
SIFT | D | D | D | D | D | D | D | T | D | D | D | D | D | D |
gnomAD MAF | 0 | 3.98e-6 | 0 | 0 | 4.95e-5 | 3.98e-6 | 7.97e-6 | 1.415e-4 | 1.971e-5 | 0 | 3.184e-5 | 0 | 7.070e-6 | 5.966e-5 |
In-house MAFa | 1/171,678 | 0/171,678 | 1/171,678 | 1/171,678 | 18/257,204 | 3/212,968 | 1/229,162 | 39/262,730 | 3/179,738 | 1/181,974 | 0/38,634 | 2/222,356 | 3/149,466 | 17/244,700 |
Clinical summary | ||||||||||||||
DD | +/+/+/+/+ | + | - | +/+ | - | + | +/+/+/+/- | +/+/+ | +/+ | + | + | + | + | + |
ID | +/+/+/+/+ | + | - | +/+ | - | - | +/+/+/+/- | -/-/NA | -/NA | - | + | + | + | + |
Hearing loss | +/+/+/+/+ | + | + | +/+ | - | + | +/+/+/+/+ | +/NA/+ | +/+ | NA | + | + | + | + |
Regression | +/+/-/-/- | + | - | -/- | - | - | -/-/-/-/- | -/+/+ | -/+ | + | - | - | - | + |
Seizures | +/-/+/-/- | + | - | +/- | - | - | -/-/+/+/+ | +/+/+ | +/+ | + | + | + | + | - |
Ataxia | +/-/-/-/- | - | + | -/- | - | + | +/-/-/-/- | +/-/+ | +/+ | - | - | + | + | - |
Hypotonia | -/-/-/-/- | - | - | +/+ | - | + | +/+/-/+/- | -/-/+ | -/+ | - | + | + | + | + |
Spasticity | +/+/-/+/+ | + | - | -/- | - | - | -/-/-/-/- | +/+/- | +/- | + | - | - | - | + |
Visual impairment | -/+/+/+/- | - | NA | -/- | - | - | -/-/-/-/- | +/+/- | +/- | + | NA | + | + | + |
Absent speech | -/+/NA/+/+ | - | - | -/+ | + | + | +/+/-/-/- | +/+/- | +/- | + | NA | - | - | + |
Mortality | -/-/-/-/- | + | - | -/- | - | - | -/-/-/-/- | -/+/- | -/- | + | + | - | - | + |
Dysmorphic facial features | +/+/+/+/+ | + | - | +/+ | + | - | +/+/+/+/- | -/-/NA | -/NA | - | - | + | + | - |
Behavioral abnormalities | -/+/-/-/- | - | - | -/+ | - | - | +/+/+/+/- | -/-/NA | -/NA | - | - | + | + | - |
Leukodystrophy | +/+/+/+/- | + | + | -/+ | - | NA | +/+/-/-/- | +/+/- | +/- | + | + | - | - | - |
