Our research focuses on elucidating the disease mechanism of aminacyl-tRNA synthetase (aARS) deficiencies, as well as development of new diagnostic tools and improvement of therapeutic options.
Our recent articles
- Kok G, Tseng LA, Schene IF, et al. Treatment of ARS-deficiencies with specific amino acids. Genet Med. 2021. Epub ahead of print.
- Kok G, van Karnebeek CDM, Fuchs SA. Response to Shen and Zou. Genet Med. 2021;23(3):589-590.
- Fuchs SA, Schene IF, Kok G, et al. Aminoacyl-tRNA synthetase deficiencies in search of common themes. Genet Med. 2019;21(2):319-330.
Cases of cytosolic aARS deficiencies in literature
Last updated: 18 May 2021
AARS1
- Simons C, Griffin LB, Helman G, et al. Loss-of-function alanyl-tRNA synthetase mutations cause an autosomal-recessive early-onset epileptic encephalopathy with persistent myelination defect. Am J Hum Genet. 2015;96(4):675-681.
- Nakayama T, Wu J, Galvin-Parton P, et al. Deficient activity of alanyl-tRNA synthetase underlies an autosomal recessive syndrome of progressive microcephaly, hypomyelination, and epileptic encephalopathy. Hum Mutat. 2017;38(10):1348-1354.
- Marten LM, Brinkert F, Smith DEC, Prokisch H, Hempel M, Santer R. Recurrent acute liver failure in alanyl-tRNA synthetase-1 (AARS1) deficiency. Mol Genet Metab Reports. 2020;25:100681.
CARS1
- Kuo ME, Theil AF, Kievit A, et al. Cysteinyl-tRNA Synthetase Mutations Cause a Multi-System, Recessive Disease That Includes Microcephaly, Developmental Delay, and Brittle Hair and Nails. Am J Hum Genet. 2019;104(3):520-529.
DARS1
- Taft RJ, Vanderver A, Leventer RJ, et al. Mutations in DARS cause hypomyelination with brain stem and spinal cord involvement and leg spasticity. Am J Hum Genet. 2013;92(5):774-780.
FARSA
- Krenke K, Szczałuba K, Bielecka T, et al. FARSA mutations mimic phenylalanyl-tRNA synthetase deficiency caused by FARSB defects. Clin Genet. 2019;96(5):468-472.
- Schuch LA, Forstner M, Rapp CK, et al. FARS1-related disorders caused by bi-allelic mutations in cytosolic phenylalanyl-tRNA synthetase genes: Look beyond the lungs! Clin Genet. 2021;99(6):789-801.
FARSB
- Antonellis A, Oprescu SN, Griffin LB, Heider A, Amalfitano A, Innis JW. Compound heterozygosity for loss-of-function FARSB variants in a patient with classic features of recessive aminoacyl-tRNA synthetase-related disease. Hum Mutat. 2018;39(6):834-840.
- Zadjali F, Al-Yahyaee A, Al-Nabhani M, et al. Homozygosity for FARSB mutation leads to Phe-tRNA synthetase-related disease of growth restriction, brain calcification, and interstitial lung disease. Hum Mutat. 2018;39(10):1355-1359.
- Xu Z, Lo W-S, Beck DB, et al. Bi-allelic Mutations in Phe-tRNA Synthetase Associated with a Multi-system Pulmonary Disease Support Non-translational Function. Am J Hum Genet. 2018;103(1):100-114.
- Schuch LA, Forstner M, Rapp CK, et al. FARS1-related disorders caused by bi-allelic mutations in cytosolic phenylalanyl-tRNA synthetase genes: Look beyond the lungs! Clin Genet. 2021;99(6):789-801.
- Kok G, Tseng LA, Schene IF, et al. Treatment of ARS-deficiencies with specific amino acids. Genet Med. 2021. Epub ahead of print.
GARS1
- McMillan HJ, Schwartzentruber J, Smith A, et al. Compound heterozygous mutations in glycyl-tRNA synthetase are a proposed cause of systemic mitochondrial disease. BMC Med Genet. 2014;15(1):36.
- Nafisinia M, Riley LG, Gold WA, et al. Compound heterozygous mutations in glycyl-tRNA synthetase (GARS) cause mitochondrial respiratory chain dysfunction. Reddy H, ed. PLoS One. 2017;12(6):e0178125.
- Oprescu SN, Chepa-Lotrea X, Takase R, et al. Compound heterozygosity for loss-of-function GARS variants results in a multisystem developmental syndrome that includes severe growth retardation. Hum Mutat. 2017;38(10):1412-1420.
HARS1
- Puffenberger EG, Jinks RN, Sougnez C, et al. Genetic mapping and exome sequencing identify variants associated with five novel diseases. Janecke AR, ed. PLoS One. 2012;7(1):e28936.
- Galatolo D, Kuo ME, Mullen P, et al. Bi-allelic mutations in HARS1 severely impair histidyl-tRNA synthetase expression and enzymatic activity causing a novel multisystem ataxic syndrome. Hum Mutat. 2020;41(7):1232-1237.
IARS1
- Kopajtich R, Murayama K, Janecke AR, et al. Biallelic IARS Mutations Cause Growth Retardation with Prenatal Onset, Intellectual Disability, Muscular Hypotonia, and Infantile Hepatopathy. Am J Hum Genet. 2016;99(2):414-422.
- Orenstein N, Weiss K, Oprescu SN, et al. Bi-allelic IARS mutations in a child with intra-uterine growth retardation, neonatal cholestasis, and mild developmental delay. Clin Genet. 2017;91(6):913-917.
- Fuchs SA, Schene IF, Kok G, et al. Aminoacyl-tRNA synthetase deficiencies in search of common themes. Genet Med. 2019;21(2):319-330.
- Fagbemi A, Newman WG, Tangye SG, Hughes SM, Cheesman E, Arkwright PD. Refractory very early-onset inflammatory bowel disease associated with cytosolic isoleucyl-tRNA synthetase deficiency: A case report. World J Gastroenterol. 2020;26(15):1841-1846.
KARS1
- Santos-Cortez RLP, Lee K, Azeem Z, et al. Mutations in KARS, encoding Lysyl-tRNA synthetase, cause autosomal-recessive nonsyndromic hearing impairment DFNB89. Am J Hum Genet. 2013;93(1):132-140.
- McMillan HJ, Humphreys P, Smith A, et al. Congenital Visual Impairment and Progressive Microcephaly Due to Lysyl–Transfer Ribonucleic Acid (RNA) Synthetase ( KARS ) Mutations. J Child Neurol. 2015;30(8):1037-1043.
- Verrigni D, Diodato D, Di Nottia M, et al. Novel mutations in KARS cause hypertrophic cardiomyopathy and combined mitochondrial respiratory chain defect. Clin Genet. 2017;91(6):918-923.
- Ruzzenente B, Assouline Z, Barcia G, et al. Inhibition of mitochondrial translation in fibroblasts from a patient expressing the KARS p.(Pro228Leu) variant and presenting with sensorineural deafness, developmental delay, and lactic acidosis. Hum Mutat. 2018;39(12):2047-2059.
- 1. Van Der Knaap MS, Bugiani M, Mendes MI, et al. Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy. Neurology. 2019;92(11):E1225-E1237.
- Fuchs SA, Schene IF, Kok G, et al. Aminoacyl-tRNA synthetase deficiencies in search of common themes. Genet Med. 2019;21(2):319-330.
- Scheidecker S, Bär S, Stoetzel C, et al. Mutations in KARS cause a severe neurological and neurosensory disease with optic neuropathy. Hum Mutat. 2019;40(10):1826-1840.
LARS1
- Casey JP, McGettigan P, Lynam-Lennon N, et al. Identification of a mutation in LARS as a novel cause of infantile hepatopathy. Mol Genet Metab. 2012;106(3):351-358.
- Casey JP, Slattery S, Cotter M, et al. Clinical and genetic characterisation of infantile liver failure syndrome type 1, due to recessive mutations in LARS. J Inherit Metab Dis. 2015;38(6):1085-1092.
- Peroutka C, Salas J, Britton J, et al. Severe neonatal manifestations of infantile liver failure syndrome type 1 caused by cytosolic leucine-tRNA synthetase deficiency. JIMD Reports. 2019;45:71-76.
- Fuchs SA, Schene IF, Kok G, et al. Aminoacyl-tRNA synthetase deficiencies in search of common themes. Genet Med. 2019;21(2):319-330.
- Tabolacci E, Molinario C, Marangi G, et al. Infantile Liver Failure Syndrome 1 associated with a novel variant of the LARS1 gene: Clinical, genetic, and functional characterization. Clin Genet. 2021;99(4):601-603.
- Lenz D, Smith DEC, Crushell E, et al. Genotypic diversity and phenotypic spectrum of infantile liver failure syndrome type 1 due to variants in LARS1. Genet Med. 2020;22(11):1863-1873.
MARS1
- van Meel E, Wegner DJ, Cliften P, et al. Rare recessive loss-of-function methionyl-tRNA synthetase mutations presenting as a multi-organ phenotype. BMC Med Genet. 2013;14(1):106.
- Hadchouel A, Wieland T, Griese M, et al. Biallelic mutations of methionyl-tRNA synthetase cause a specific type of pulmonary alveolar proteinosis prevalent on Réunion Island. Am J Hum Genet. 2015;96(5):826-831.
- Sun Y, Hu G, Luo J, et al. Mutations in methionyl-tRNA synthetase gene in a Chinese family with interstitial lung and liver disease, postnatal growth failure and anemia. J Hum Genet. 2017;62(6):647-651.
- Abuduxikuer K, Feng JY, Lu Y, Xie XB, Chen L, Wang JS. Novel methionyl-tRNA synthetase gene variants/ phenotypes in interstitial lung and liver disease: A case report and review of literature. World J Gastroenterol. 2018;24(36):4208-4216.
- Alzaid M, Alshamrani A, Harbi ASA, Alenzi A, Mohamed S. Methionyl-tRNA synthetase novel mutation causes pulmonary alveolar proteinosis. Saudi Med J. 2019;40(2):195-198.
- Lenz D, Stahl M, Seidl E, et al. Rescue of respiratory failure in pulmonary alveolar proteinosis due to pathogenic MARS1 variants. Pediatr Pulmonol. 2020;55(11):3057-3066.
NARS1
- Manole A, Efthymiou S, O’Connor E, et al. De Novo and Bi-allelic Pathogenic Variants in NARS1 Cause Neurodevelopmental Delay Due to Toxic Gain-of-Function and Partial Loss-of-Function Effects. Am J Hum Genet. 2020;107(2):311-324.
QARS1
- Zhang X, Ling J, Barcia G, et al. Mutations in QARS, encoding glutaminyl-trna synthetase, cause progressive microcephaly, cerebral-cerebellar atrophy, and intractable seizures. Am J Hum Genet. 2014;94(4):547-558.
- Salvarinova R, Ye CX, Rossi A, et al. Expansion of the QARS deficiency phenotype with report of a family with isolated supratentorial brain abnormalities. Neurogenetics. 2015;16(2):145-149.
- Kodera H, Osaka H, Iai M, et al. Mutations in the glutaminyl-tRNA synthetase gene cause early-onset epileptic encephalopathy. J Hum Genet. 2015;60(2):97-101.
- Leshinsky-Silver E, Ling J, Wu J, et al. Severe growth deficiency, microcephaly, intellectual disability, and characteristic facial features are due to a homozygous QARS mutation. Neurogenetics. 2017;18(3):141-146.
- Johannesen KM, Mitter D, Janowski R, et al. Defining and expanding the phenotype of QARS-associated developmental epileptic encephalopathy. Neurol Genet. 2019;5(6):e373.
- Fuchs SA, Schene IF, Kok G, et al. Aminoacyl-tRNA synthetase deficiencies in search of common themes. Genet Med. 2019;21(2):319-330.
RARS1
- Wolf NI, Salomons GS, Rodenburg RJ, et al. Mutations in RARS cause hypomyelination. Ann Neurol. 2014;76(1):134-139.
- Mendes MI, Green LMC, Bertini E, et al. RARS1-related hypomyelinating leukodystrophy: Expanding the spectrum. Ann Clin Transl Neurol. 2020;7(1):83-93.
SARS1
- Musante L, Püttmann L, Kahrizi K, et al. Mutations of the aminoacyl-tRNA-synthetases SARS and WARS2 are implicated in the etiology of autosomal recessive intellectual disability. Hum Mutat. 2017;38(6):621-636.
- Kok G, Tseng LA, Schene IF, et al. Treatment of ARS-deficiencies with specific amino acids. Genet Med. 2021. Epub ahead of print.
TARS1
- Theil AF, Botta E, Raams A, et al. Bi-allelic TARS Mutations Are Associated with Brittle Hair Phenotype. Am J Hum Genet. 2019;105(2):434-440.
VARS1
- Karaca E, Harel T, Pehlivan D, et al. Genes that Affect Brain Structure and Function Identified by Rare Variant Analyses of Mendelian Neurologic Disease. Neuron. 2015;88(3):499-513.
- Stephen J, Nampoothiri S, Banerjee A, et al. Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy. Hum Genet. 2018;137(4):293-303.
- Friedman J, Smith DE, Issa MY, et al. Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy. Nat Commun. 2019;10(1):707.
YARS1
- Nowaczyk MJM, Huang L, Tarnopolsky M, et al. A novel multisystem disease associated with recessive mutations in the tyrosyl-tRNA synthetase (YARS) gene. Am J Med Genet Part A. 2017;173(1):126-134.
- Williams KB, Brigatti KW, Puffenberger EG, et al. Homozygosity for a mutation affecting the catalytic domain of tyrosyl-tRNA synthetase (YARS) causes multisystem disease. Hum Mol Genet. 2019;28(4):525-538.
- Zeiad RKHM, Ferren EC, Young DD, et al. A Novel Homozygous Missense Mutation in the YARS Gene: Expanding the Phenotype of YARS Multisystem Disease . J Endocr Soc. 2021;5(2).