Novel, Compound Heterozygous, Single-Nucleotide Variants in MARS2 Associated with Developmental Delay, Poor Growth, and Sensorineural Hearing Loss

Human Mutation

Volumn 36, Issue 6, 2015, Pages 587-592

  Webb, Bryn D ^a   Wheeler, Patricia G ^b   Hagen, Jacob J ^a   Cohen, Ninette ^a   Linderman, Michael D ^a   Diaz, George A ^a   Naidich, Thomas P ^a   Rodenburg, Richard J ^c   Houten, Sander M ^a   Schadt, Eric E ^a  

^a MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^b NEMOURS CHILDREN S HOSPITAL   (United States)

^c RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

MARS2; Mitochondrial amino acyl tRNA synthetase; Mitochondrial translation

Indexed keywords

AMINO ACID TRANSFER RNA LIGASE; CREATINE KINASE; CYTOCHROME C OXIDASE; GROWTH HORMONE; OXCARBAZEPINE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE); METHIONINE TRANSFER RNA LIGASE;

ANTHROPOMETRIC PARAMETERS; ARTICLE; ASPIRATION PNEUMONIA; BODY MASS; BRAIN ATROPHY; BRAIN HEMORRHAGE; CALORIC INTAKE; CASE REPORT; CHRONIC CONSTIPATION; DEVELOPMENTAL DISORDER; ELECTROENCEPHALOGRAM; ENZYME ACTIVITY; GENE; GENE IDENTIFICATION; GENE MUTATION; GENETIC ASSOCIATION; GENETIC TRANSCRIPTION; GENETIC VARIABILITY; GROWTH DISORDER; GROWTH HORMONE DEFICIENCY; HEARING AID; HETEROZYGOTE; HUMAN; HUMAN TISSUE; MALE; MARS2 GENE; NEUROIMAGING; NEWBORN; NUCLEAR MAGNETIC RESONANCE IMAGING; PERCEPTION DEAFNESS; PHENOTYPE; PRIORITY JOURNAL; SEIZURE; SINGLE NUCLEOTIDE POLYMORPHISM; SKIN BIOPSY; STOMACH FUNDOPLICATION; TRANSMISSION ELECTRON MICROSCOPY; AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; BRAIN; CHEMISTRY; DEVELOPMENTAL DISABILITIES; GENETIC ASSOCIATION STUDY; GENETICS; GROWTH DISORDERS; HEARING LOSS, SENSORINEURAL; MITOCHONDRIAL GENE; PATHOLOGY; PEDIGREE; PRESCHOOL CHILD;

AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; BRAIN; CHILD, PRESCHOOL; DEVELOPMENTAL DISABILITIES; GENES, MITOCHONDRIAL; GENETIC ASSOCIATION STUDIES; GROWTH DISORDERS; HEARING LOSS, SENSORINEURAL; HETEROZYGOTE; HUMANS; MAGNETIC RESONANCE IMAGING; MALE; METHIONINE-TRNA LIGASE; PEDIGREE; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 84929502811     PISSN: 10597794     EISSN: 10981004     Source Type: Journal    
DOI: 10.1002/humu.22781     Document Type: Article

References (19)

1. Bayat V, Thiffault I, Jaiswal M, Tetreault M, Donti T, Sasarman F, Bernard G, Demers-Lamarche J, Dicaire MJ, Mathieu J, Vanasse M, Bouchard JP, et al. 2012. Mutations in the mitochondrial methionyl-tRNA synthetase cause a neurodegenerative phenotype in flies and a recessive ataxia (ARSAL) in humans. PLoS Biol 10:e1001288.
2. Belostotsky R, Ben-Shalom E, Rinat C, Becker-Cohen R, Feinstein S, Zeligson S, Segel R, Elpeleg O, Nassar S, Frishberg Y. 2011. Mutations in the mitochondrial seryl-tRNA synthetase cause hyperuricemia, pulmonary hypertension, renal failure in infancy and alkalosis, HUPRA syndrome. Am J Hum Genet 88:193-200.
3. Bricout M, Grevent D, Lebre AS, Rio M, Desguerre I, DeLonlay P, Valayannopoulos V, Brunelle F, Rotig A, Munnich A, Boddaert N. 2014. Brain imaging in mitochondrial chain deficiency: combination of brain MRI features as a useful tool for genotype/phenotype correlations. J Med Genet 51:429-435.
4. Edvardson S, Shaag A, Kolesnikova O, Gomori JM, Tarassov I, Einbinder T, Saada A, Elpeleg O. 2007. Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia. Am J Hum Genet 81:857-862.
5. Elo JM, Yadavalli SS, Euro L, Isohanni P, Gotz A, Carroll CJ, Valanne L, Alkuraya FS, Uusimaa J, Paetau A, Caruso EM, Pihko H, et al. 2012. Mitochondrial phenylalanyl-tRNA synthetase mutations underlie fatal infantile Alpers encephalopathy. Hum Mol Genet 21:4521-4529.
6. Gotz A, Tyynismaa H, Euro L, Ellonen P, Hyotylainen T, Ojala T, Hamalainen RH, Tommiska J, Raivio T, Oresic M, Karikoski R, Tammela O, et al. 2011. Exome sequencing identifies mitochondrial alanyl-tRNA synthetase mutations in infantile mitochondrial cardiomyopathy. Am J Hum Genet 88:635-642.
7. Houten SM, Denis S, TeBrinke H, Jongejan A, vanKampen AH, Bradley EJ, Baas F, Hennekam RC, Millington DS, Young SP, Frazier DM, Gucsavas-Calikoglu M, et al. 2014. Mitochondrial NADP(H) deficiency due to a mutation in NADK2 causes dienoyl-CoA reductase deficiency with hyperlysinemia. Hum Mol Genet 23:5009-5016.
8. Kircher M, Witten DM, Jain P, O'Roak BJ, Cooper GM, Shendure J. 2014. A general framework for estimating the relative pathogenicity of human genetic variants. Nat Genet 46:310-315.
9. Konovalova S, Tyynismaa H. 2013. Mitochondrial aminoacyl-tRNA synthetases in human disease. Mol Genet Metab 108:206-211.
10. Linderman MD, Brandt T, Edelmann L, Jabado O, Kasai Y, Kornreich R, Mahajan M, Shah H, Kasarskis A, Schadt EE. 2014. Analytical validation of whole exome and whole genome sequencing for clinical applications. BMC Med Genomics 7:20.
11. Pierce SB, Chisholm KM, Lynch ED, Lee MK, Walsh T, Opitz JM, Li W, Klevit RE, King MC. 2011. Mutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome. Proc Natl Acad Sci USA 108:6543-6548.
12. Pierce SB, Gersak K, Michaelson-Cohen R, Walsh T, Lee MK, Malach D, Klevit RE, King MC, Levy-Lahad E. 2013. Mutations in LARS2, encoding mitochondrial leucyl-tRNA synthetase, lead to premature ovarian failure and hearing loss in Perrault syndrome. Am J Hum Genet 92:614-620.
13. Riley LG, Cooper S, Hickey P, Rudinger-Thirion J, McKenzie M, Compton A, Lim SC, Thorburn D, Ryan MT, Giege R, Bahlo M, Christodoulou J. 2010. Mutation of the mitochondrial tyrosyl-tRNA synthetase gene, YARS2, causes myopathy, lactic acidosis, and sideroblastic anemia-MLASA syndrome. Am J Hum Genet 87:52-59.
14. Rodenburg RJ. 2011. Biochemical diagnosis of mitochondrial disorders. J Inherit Metab Dis 34:283-292.
15. Scheper GC, vander Klok T, vanAndel RJ, vanBerkel CG, Sissler M, Smet J, Muravina TI, Serkov SV, Uziel G, Bugiani M, Schiffmann R, Krageloh-Mann I, et al. 2007. Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. Nat Genet 39:534-539.
16. Spencer AC, Heck A, Takeuchi N, Watanabe K, Spremulli LL. 2004. Characterization of the human mitochondrial methionyl-tRNA synthetase. Biochemistry 43:9743-9754.
17. Steenweg ME, Ghezzi D, Haack T, Abbink TE, Martinelli D, vanBerkel CG, Bley A, Diogo L, Grillo E, Te Water Naude J, Strom TM, Bertini E, et al. 2012. Leukoencephalopathy with thalamus and brainstem involvement and high lactate 'LTBL' caused by EARS2 mutations. Brain 135(Pt 5):1387-1394.
18. Thiffault I, Rioux MF, Tetreault M, Jarry J, Loiselle L, Poirier J, Gros-Louis F, Mathieu J, Vanasse M, Rouleau GA, Bouchard JP, Lesage J, et al. 2006. A new autosomal recessive spastic ataxia associated with frequent white matter changes maps to 2q33-34. Brain 129(Pt 9):2332-2340.
19. Wolf NI, Smeitink JA. 2002. Mitochondrial disorders: a proposal for consensus diagnostic criteria in infants and children. Neurology 59:1402-1405.