DISEASE: Neurodevelopmental disorder with aminoacyl-tRNA synthetase defect
Entry
H02709 Disease
Name
Neurodevelopmental disorder with aminoacyl-tRNA synthetase defect
Subgroup
NED with microcephaly, ataxia, and seizures (NEDMAS) NED with microcephaly, seizures, and cortical atrophy (NDMSCA) NED with microcephaly, impaired language, epilepsy, and gait abnormalities (NEDMILEG) Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures (NEMMLAS) NED with microcephaly and speech delay, with or without brain abnormalities (NEDMSBA)
Description
The aminoacyl-tRNA synthetases (aaRSs) are an evolutionarily ancient family of enzymes that catalyze the esterification reaction linking a transfer RNA (tRNA) with its cognate amino acid matching the anticodon triplet of the tRNA. To date, some neurodevelopmental disorders caused by mutations in aaRS genes have been described. Symptoms of these disorders include intellectual disability, delayed language development and ability to walk, microcephaly, movement disorders, and in some cases seizures.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Multiple developmental anomalies or syndromes
LD20 Syndromes with central nervous system anomalies as a major feature
H02709 Neurodevelopmental disorder with aminoacyl-tRNA synthetase defect
Stephen J, Nampoothiri S, Banerjee A, Tolman NJ, Penninger JM, Elling U, Agu CA, Burke JD, Devadathan K, Kannan R, Huang Y, Steinbach PJ, Martinis SA, Gahl WA, Malicdan MCV
Title
Loss of function mutations in VARS encoding cytoplasmic valyl-tRNA synthetase cause microcephaly, seizures, and progressive cerebral atrophy.
Manole A, Efthymiou S, O'Connor E, Mendes MI, Jennings M, Maroofian R, Davagnanam I, Mankad K, Lopez MR, Salpietro V, Harripaul R, Badalato L, Walia J, Francklyn CS, Athanasiou-Fragkouli A, Sullivan R, Desai S, Baranano K, Zafar F, Rana N, Ilyas M, Horga A, Kara M, Mattioli F, Goldenberg A, Griffin H, Piton A, Henderson LB, Kara B, Aslanger AD, Raaphorst J, Pfundt R, Portier R, Shinawi M, Kirby A, Christensen KM, Wang L, Rosti RO, Paracha SA, Sarwar MT, Jenkins D, Ahmed J, Santoni FA, Ranza E, Iwaszkiewicz J, Cytrynbaum C, Weksberg R, Wentzensen IM, Guillen Sacoto MJ, Si Y, Telegrafi A, Andrews MV, Baldridge D, Gabriel H, Mohr J, Oehl-Jaschkowitz B, Debard S, Senger B, Fischer F, van Ravenwaaij C, Fock AJM, Stevens SJC, Bahler J, Nasar A, Mantovani JF, Manzur A, Sarkozy A, Smith DEC, Salomons GS, Ahmed ZM, Riazuddin S, Riazuddin S, Usmani MA, Seibt A, Ansar M, Antonarakis SE, Vincent JB, Ayub M, Grimmel M, Jelsig AM, Hjortshoj TD, Karstensen HG, Hummel M, Haack TB, Jamshidi Y, Distelmaier F, Horvath R, Gleeson JG, Becker H, Mandel JL, Koolen DA, Houlden H
Title
De Novo and Bi-allelic Pathogenic Variants in NARS1 Cause Neurodevelopmental Delay Due to Toxic Gain-of-Function and Partial Loss-of-Function Effects.
