The Mitochondrial Aminoacyl tRNA Synthetases: Genes and Syndromes

Table 1

Clinical and radiological phenotypes associated with different aaRS2 mutations.

	OMIM (gene)	Protein	Clinical picture	OMIM; (phenotype)	Age at onset	MRI pattern	Reported cases	References
DARS2	*610956	mt aspartyl-tRNA synthetase	Cerebellar ataxia, spasticity, dorsal column dysfunction, cognitive impairment	#611105	Childhood/adulthood	Leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation (LBSL)	>30 families	[17–24]
RARS2	*611524	mt arginyl-tRNA synthetase	Encephalopathy with lethargia, hypotonia, epilepsy, and microcephaly	#611523	Perinatal	Pontocerebellar hypoplasia, brain stem thinning	>10 families	[25–28]
YARS2	*610957	mt tyrosyl-tRNA synthetase	Myopathy, lactic acidosis, and sideroblastic anemia (MLASA)	#613561	Childhood	None	3 families	[29–31]
SARS2	*612804	mt seryl-tRNA synthetase	Hyperuricemia, pulmonary hypertension, renal failure, and alkalosis (HUPRA)	#613845	Perinatal	None	4 families	[32]
AARS2	*612035	mt alanyl-tRNA synthetase	Hypertrophic cardiomyopathy, delayed motor development, cerebellar ataxia	#612035	Childhood	None	7 families	[33, 34]
MARS2	*609728	mt methionyl-tRNA synthetase	Autosomal recessive spastic ataxia	/	Childhood/adulthood	Cerebellar atrophy and white matter alterations, thin corpus callosum	1 family	[35]
HARS2	*600783	mt histidyl-tRNA synthetase	Sensorineural hearing loss and ovarian dysgenesis (Perrault syndrome)	#614926	Childhood/adulthood	None	1 family	[36]
LARS2	*604544	mt leucyl-tRNA synthetase	Sensorineural hearing loss and ovarian dysgenesis (Perrault syndrome)	#615300	Childhood/adulthood	None	1 family	[37]
FARS2	*611592	mt phenylalanine-tRNA synthetase	Epileptic encephalopathy, liver disease, and lactic acidosis	#614946	Perinatal	Cerebral and cerebellar, brain stem and basal ganglia atrophy	3 families	[38, 39]
EARS2	*612799	mt glutamyl-tRNA synthetase	Global developmental delay or arrest, epilepsy, dystonia, spasticity, and high lactate	#614924	Early childhood	Leukoencephalopathy with thalamus and brain stem involvement and high lactate (LTBL)	12 families	[40, 41]
VARS2	*612802	mt valyl-tRNA synthetase	Psychomotor delay, seizures, facial dysmorphism, lactic acidosis	/	Childhood	Hyperintense lesions in the insula and frontotemporal right cortex	1 family	[42]
TARS2	*612805	mt threonyl-tRNA synthetase	Psychomotor delay, hypotonia	/	Perinatal/early childhood	Thin corpus callosum, bilateral lesion of the pallidum	1 family	[42]
GARS	*600287	Glycyl-tRNA synthetase	Charcot-Marie-Tooth (CMT) disease 2D or distal hereditary motor neuropathy VA	#601472, #600794	Childhood/adulthood	None	>8 families	[43–50]
KARS	*601421	Lysyl-tRNA synthetase	Autosomal recessive CMT (intermediate, B)	#613641	Childhood/adulthood	None	4 families	[51, 52]