Table 1 Overview of FARS2 variations related to human disease
Variations | Onset | Developmental delay | Enzyme function | OXPHOS biochemistry | References | |
|---|---|---|---|---|---|---|
Early-onset epileptic encephalopathy | ||||||
1 | c.251 A > C (p.H84P); | 10 m | + | Decreased mtPheRS abundance | ↓CI and CIV in fibroblasts | [17] |
c.1256G > A (p.R419H) | ||||||
2 | c.431 A > G (p.Y144C) | in infancy | + | Affected mtPheRS aminoacylation activity | NA | |
3 | c.431 A > G (p.Y144C); | in infancy | NA | NA | NA | [19] |
c.530 T > A (p.V177D) | ||||||
4 | c.667 C > T (p.R223C) | 5 m | + | NA | NA | [20] |
5 | c.925G > A (p.G309S) | 3/4m | + | NA | Combined OXPHO deficiency | [21] |
6 | c.973G > T (p.D325Y) | 6 m | + | Disappared mtPheRS aminoacylation activity | ↓CIV defect in myoblasts | [22] |
7 | c.973G > T (p.D325Y) | 6 m | + | NA | NA | [18] |
chr6:del(5,193,613– 5,281,294) | ||||||
8 | c.986T > C (p.I329T) | 2d | + | Affected mtPheRS aminoacylation activity | NA | [5] |
c.1172 A > T (p.D391V) | ||||||
9 | c.989G > A (p.R330H) | 6w | + | Decreased mtPheRS abundance | ↓CIV in muscle and fibroblasts | [17] |
c.1113G > T (p.L371F) | ||||||
10 | c.1156 C > G (p.R386G) | 3/7m | + | NA | ↓CI and CIV in fibroblasts | [23] |
chr6:del(5,262,296–5,395,849) | ||||||
11 | c.1255 C > T (p.R419C); | in infancy | + | NA | NA | [18] |
chr6:del(5,610,223– 5,726,369) | ||||||
12 | c.1256G > A (p.R419H) | < 1 m | + | Decreased mtPheRS abundance | ↓CI in muscle;↓CI and CIV in fibroblasts | [17] |
c.1269_1276del (p.S426*) | ||||||
Later-onset spastic paraplegia | ||||||
13 | c.422G > A (p.G141E) | 18/24m | NA | NA | NA | [24] |
chr6:del(5,564,777–5,639,774) | ||||||
14 | c.424G > T (p.D142Y) | 3y | - | Decreased mtPheRS aminoacylation activity | NA | [11] |
15 | c.461 C > T (p.A154V) | 6 m | + | Decreased mtPheRS aminoacylation activity | ↓CIV in muscle and fibroblasts;↓CI in fibroblasts | [25] |
c.1082 C > T (p.P361L) | ||||||
16 | c.476 A > C (p.H159P) | 1/2y | + | NA | NA | [19] |
c.1255 C > T (p.R419C) | ||||||
17 | c.521_523del (p.V174del) | 10Â m | + | NA | NA | [25] |
c.1082 C > T (p.P361L) | ||||||
18 | c.646 C > T (p.Q216*) | 2.5y | - | NA | NA | [26] |
c.407 C > A (p.P136H) | Decreased mtPheRS aminoacylation activity | |||||
19 | c.1082 C > T (p.P361L) | 5y | - | NA | NA | [25] |
ex. 1–2 del | ||||||
20 | p.D364G | teenage | NA | Disappared mtPheRS aminoacylation activity | NA | [12] |
Juvenile-onset refractory epilepsy | ||||||
21 | c.253 C > G (p.P85A) | 8y | + | Decrease mtPheRS stability | NA | [27] |
c.403 C > G (p.H135D) | Decrease mtPheRS aminoacylation activity | |||||
22 | c.589G > A (p.V197M) | 12y | - | NA | NA | [28] |
c.1205T > C (p.F402S) | ||||||
23 | c.589G > A (p.V197M) | 17y | - | NA | ↑CII and CIV in muscle | [10] |
chr6:del(5,368,803–5,369,415) | ||||||
Onset unknown | ||||||
24 | c.467 C > T (p.T156M) | NA | NA | NA | NA | [29] |
25 | c.1275G > C (p.L425L) | NA | NA | NA | NA | [5] |
c.1277 C > T (p.S426F) | ||||||
26 | c.905-1G > A | NA | NA | NA | NA | [19] |
27 | c.457 A > G (p.R153G) | NA | NA | NA | NA | [19] |
c.925G > A (p.G309S) | ||||||