Table 3. Mutations in aminoacyl-tRNA synthetases.

Gene	Protein	Clinical presentation	Age of onset	Mode of inheritance	OMIM	References
DARS2	Aspartyl-tRNA sythetase 2	- Leukoencephalopathy with brainstem and spinal cord involvement (LBSL) - Paroxysmal exercise-induced gait ataxia	Childhood or adulthood	AR	610956	Scheper et al. (2007) [76] Isohanni et al. (2010) [77] Miyake et al. (2011) [78] van Berge et al. (2014) [79] Shimojima et al. (2017) [80] Pinto et al. (2014) [81] Synofzik et al. (2011) [82]
RARS2	Arginyl-tRNA synthetase 2	Pontocerebellar hypoplasia type 6 (PCHD-6)	Neonatal or early childhood	AR	611523	Edvardson et al. (2007) [83] Rankin et al. (2010) [84] Cassandrini et al. (2013) [85] Li et al. (2015) [86] Lühl et al. (2016) [87]
EARS2	Glutamyl-tRNA synthetase 2	Leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL); multiple congenital anomalies and multisystem dysfunction dysgenesis of corpus callosum	Congenital or infantile	AR	612799	Steenweg et al. (2012) [88] Talim et al. (2013) [89] Kevelam et al. (2016) [90] Güngör et al. (2016) [91] Şahin et al. (2016) [92]
MARS2	Methionyl-tRNA synthetase 2	Autosomal recessive spastic ataxia with leukoencephalopathy	Juvenile or adulthood	AR	609728	Bayat et al. (2012) [93] Webb et al. (2015) [94]
FARS2	Phenylalanyl-tRNA synthetase 2	Alpers syndrome, encephalopathy, epilepsy, lactic acidosis, spastic paraplegia	Neonatal or infantile	AR	611592	Elo et al. (2012) [95] Shamseldin et al. (2012) [96] Yang et al. (2016) [97]
AARS2	Alanyl-tRNA synthetase 2	- Hypertrophic cardiomyopathy - Ovario-leukodystrophy - Leukoencephalopathy with axonal spheroids and pigmented glia (ALSP)	Infantile to adulthood	AR	614096	Götz et al. (2011) [98] Taylor et al. (2014) [99] Dallabona et al. (2014) [100] Lynch et al. (2016) [101] Szpisjak et al. (2017) [102]
YARS2	Tyrosyl-tRNA synthetase	MLASA2, gastrointestinal difficulties, cardiomyopathy	Infantile	AR	613561	Riley et al. (2010) [67] Sasarman et al. (2012) [103] Shahni et al. (2013) [104] Riley et al. (2013) [105] Nakajima et al. (2014) [106]
SARS	Seryl-tRNA synthetase 2	- HUPRA syndrome (hyperuricemia, pulmonary hypertension, renal failure in infancy, and alkalosis) - Progressive spastic paresis	Infantile	AR	613845	Belostotsky et al. (2011) [107] Linnankivi et al. (2016) [108]
HARS2	Histidyl-tRNA synthetase 2	Perrault syndrome (sensorineural deafness, ovarian dysgenesis)	Juvenile or adulthood	AR	600783	Pierce et al. (2011) [109]
LARS2	Leucyl-tRNA synthetase	Perrault syndrome (sensorineural deafness, ovarian dysgenesis) hydrops, lactic acidosis, and sideroblastic anemia	Juvenile neonatal	AR	604544	Pierce et al. (2013) [110] Soldà et al. (2016) [111] Demain et al. (2017) [112] Riley et al. (2016) [113]
TARS2	Threonyl-tRNA synthetas	Mitochondrial encephalomyopathy Axial hypotonia and limb hypertonia, psychomotor delay, and high levels of blood lactate	Infantile	AR	612805	Diodato et al. (2014) [114]
NARS2	Asparginyl-tRNA synthetase	Non-syndromic deafness, Leigh syndrome, Alpers syndrome, infantile onset neurodegenerative disorder	Infantile	AR	612803	Sofou et al. (2015) [115] Vanlander et al. (2015) [116] Simon et al. (2015) [117] Mizuguchi et al. (2017) [118]
CARS2	Cysteinyl-tRNA synthetas	Combined oxidative phosphorylation deficiency-27 (COXPD27); severe epileptic encephalopathy and complex movement disorders	Juvenile	AR	612800	Coughlin et al. (2015) [119]
IARS2	Ileucyl-tRNA synthetase	- Skeletal dysplasia, infantile cataract, congenital neurotrophic keratitis, orbital myopathy, Leigh syndrome - CAGSSS syndrome	Adulthood or infantile	AR	616007 612801	Schwartzentruber et al. (2014) [120] Moosa et al. (2017) [121]
VARS2	Valyl-tRNa synthetase	Mitochondrial encephalomyopathy: psychomotor delay, epilepsy, mental retardation, growth hormone deficiency, hypogonadism	Juvenile	AR	612802	Diodato et al. (2014) [114] Baertling et al. (2017) [122] Alsemari et al. (2017) [123]
WARS2	Tryptophanyl-tRNA synthetase	- Autosomal recessive intellectual disability - Mitochondrial encephalopathy - Infantile-onset Parkinsonism	Infantile or juvenile	AR	604733	Musante et al. (2017) [124] Wortmann et al. (2017) [125] Theisen et al. (2017) [126] Burke et al. (2017) [127]
PARS2	Prolyl-tRNA synthetase	Non-syndromic hearing loss, Leigh syndrome, intellectual disability with epilepsy and severe myopathy, seizure	Infantile	AR	612036	Sofou et al. (2015) [128] Mizuguchi et al. (2017) [118]
GARS	Glycil-tRNA synthetase	- Charcot-Marie-Tooth disease, type 2D - Neuropathy, distal hereditary motor, type VA - Multisystem developmental delay, growth retardation- Lactic acidosis, cardiomyopathy, exercise intolerance	Adulthood, early childhood	AD AR	601472 600794	Antonellis et al. (2003) [129] Oprescu et al. (2017) [130] Nafisinia et al. (2017) [131] McMillan et al. (2014) [132]
KARS	Lysyl-tRNA synthetases	- Charcot-Marie-Tooth disease, recessive intermediate, B - Deafness, autosomal recessive 89 - Visual impairment and progressive microcephaly - Hypertrophic cardiomyopathy and combined mitochondrial respiratory chain defect	Adult, infantile, childhood	AR	613641 613916	Kohda et al. (2016) [133] Verrigini et al. (2017) [134] McMillan et al. (2015) [135] Santos-Cortez et al. (2013) [136] McLaughlin et al. (2010) [137]

OMIM, Online Mendelian Inheritance in Man; AR, autosomal recessive; AD, autosomal dominant.