[{"intvolume":"        43","status":"public","quality_controlled":"1","publication":"Human Mutation","publisher":"Wiley","date_created":"2023-09-20T20:58:24Z","extern":"1","month":"10","page":"1472-1489","doi":"10.1002/humu.24435","ddc":["570"],"language":[{"iso":"eng"}],"keyword":["autosomal recessive","biallelic variants","C","elegans","translation initiation sites","tryptophanyl-tRNA synthetase 1 (WARS1)","WHEP domain","zebrafish"],"author":[{"full_name":"Lin, Sheng-Jia","first_name":"Sheng-Jia","last_name":"Lin"},{"full_name":"Vona, Barbara","first_name":"Barbara","last_name":"Vona"},{"first_name":"Hillary M.","full_name":"Porter, Hillary M.","last_name":"Porter"},{"last_name":"Izadi","full_name":"Izadi, Mahmoud","first_name":"Mahmoud"},{"last_name":"Huang","first_name":"Kevin","full_name":"Huang, Kevin","id":"3b3d2888-1ff6-11ee-9fa6-8f209ca91fe3","orcid":"0000-0002-2512-7812"},{"last_name":"Lacassie","full_name":"Lacassie, Yves","first_name":"Yves"},{"last_name":"Rosenfeld","full_name":"Rosenfeld, Jill A.","first_name":"Jill A."},{"last_name":"Khan","full_name":"Khan, Saadullah","first_name":"Saadullah"},{"full_name":"Petree, Cassidy","first_name":"Cassidy","last_name":"Petree"},{"last_name":"Ali","first_name":"Tayyiba A.","full_name":"Ali, Tayyiba A."},{"last_name":"Muhammad","full_name":"Muhammad, Nazif","first_name":"Nazif"},{"last_name":"Khan","first_name":"Sher A.","full_name":"Khan, Sher A."},{"full_name":"Muhammad, Noor","first_name":"Noor","last_name":"Muhammad"},{"last_name":"Liu","first_name":"Pengfei","full_name":"Liu, Pengfei"},{"first_name":"Marie-Louise","full_name":"Haymon, Marie-Louise","last_name":"Haymon"},{"first_name":"Franz","full_name":"Rueschendorf, Franz","last_name":"Rueschendorf"},{"full_name":"Kong, Il-Keun","first_name":"Il-Keun","last_name":"Kong"},{"last_name":"Schnapp","first_name":"Linda","full_name":"Schnapp, Linda"},{"full_name":"Shur, Natasha","first_name":"Natasha","last_name":"Shur"},{"last_name":"Chorich","first_name":"Lynn","full_name":"Chorich, Lynn"},{"last_name":"Layman","full_name":"Layman, Lawrence","first_name":"Lawrence"},{"full_name":"Haaf, Thomas","first_name":"Thomas","last_name":"Haaf"},{"last_name":"Pourkarimi","full_name":"Pourkarimi, Ehsan","first_name":"Ehsan"},{"full_name":"Kim, Hyung-Goo","first_name":"Hyung-Goo","last_name":"Kim"},{"last_name":"Varshney","first_name":"Gaurav K.","full_name":"Varshney, Gaurav K."}],"type":"journal_article","day":"01","title":"Biallelic variants in WARS1 cause a highly variable neurodevelopmental syndrome and implicate a critical exon for normal auditory function","citation":{"short":"S.-J. Lin, B. Vona, H.M. Porter, M. Izadi, K. Huang, Y. Lacassie, J.A. Rosenfeld, S. Khan, C. Petree, T.A. Ali, N. Muhammad, S.A. Khan, N. Muhammad, P. Liu, M.-L. Haymon, F. Rueschendorf, I.-K. Kong, L. Schnapp, N. Shur, L. Chorich, L. Layman, T. Haaf, E. Pourkarimi, H.-G. Kim, G.K. Varshney, Human Mutation 43 (2022) 1472–1489.","apa":"Lin, S.-J., Vona, B., Porter, H. M., Izadi, M., Huang, K., Lacassie, Y., … Varshney, G. K. (2022). Biallelic variants in WARS1 cause a highly variable neurodevelopmental syndrome and implicate a critical exon for normal auditory function. <i>Human Mutation</i>. Wiley. <a href=\"https://doi.org/10.1002/humu.24435\">https://doi.org/10.1002/humu.24435</a>","ama":"Lin S-J, Vona B, Porter HM, et al. Biallelic variants in WARS1 cause a highly variable neurodevelopmental syndrome and implicate a critical exon for normal auditory function. <i>Human Mutation</i>. 2022;43(10):1472-1489. doi:<a href=\"https://doi.org/10.1002/humu.24435\">10.1002/humu.24435</a>","ista":"Lin S-J, Vona B, Porter HM, Izadi M, Huang K, Lacassie Y, Rosenfeld JA, Khan S, Petree C, Ali TA, Muhammad N, Khan SA, Muhammad N, Liu P, Haymon M-L, Rueschendorf F, Kong I-K, Schnapp L, Shur N, Chorich L, Layman L, Haaf T, Pourkarimi E, Kim H-G, Varshney GK. 2022. Biallelic variants in WARS1 cause a highly variable neurodevelopmental syndrome and implicate a critical exon for normal auditory function. Human Mutation. 43(10), 1472–1489.","ieee":"S.-J. Lin <i>et al.</i>, “Biallelic variants in WARS1 cause a highly variable neurodevelopmental syndrome and implicate a critical exon for normal auditory function,” <i>Human Mutation</i>, vol. 43, no. 10. Wiley, pp. 1472–1489, 2022.","chicago":"Lin, Sheng-Jia, Barbara Vona, Hillary M. Porter, Mahmoud Izadi, Kevin Huang, Yves Lacassie, Jill A. Rosenfeld, et al. “Biallelic Variants in WARS1 Cause a Highly Variable Neurodevelopmental Syndrome and Implicate a Critical Exon for Normal Auditory Function.” <i>Human Mutation</i>. Wiley, 2022. <a href=\"https://doi.org/10.1002/humu.24435\">https://doi.org/10.1002/humu.24435</a>.","mla":"Lin, Sheng-Jia, et al. “Biallelic Variants in WARS1 Cause a Highly Variable Neurodevelopmental Syndrome and Implicate a Critical Exon for Normal Auditory Function.” <i>Human Mutation</i>, vol. 43, no. 10, Wiley, 2022, pp. 1472–89, doi:<a href=\"https://doi.org/10.1002/humu.24435\">10.1002/humu.24435</a>."},"volume":43,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"file_date_updated":"2023-09-25T08:52:54Z","oa":1,"publication_status":"published","license":"https://creativecommons.org/licenses/by/4.0/","date_published":"2022-10-01T00:00:00Z","_id":"14356","abstract":[{"lang":"eng","text":"Aminoacyl-tRNA synthetases (ARSs) are essential enzymes for faithful assignment of amino acids to their cognate tRNA. Variants in ARS genes are frequently associated with clinically heterogeneous phenotypes in humans and follow both autosomal dominant or recessive inheritance patterns in many instances. Variants in tryptophanyl-tRNA synthetase 1 (WARS1) cause autosomal dominantly inherited distal hereditary motor neuropathy and Charcot-Marie-Tooth disease. Presently, only one family with biallelic WARS1 variants has been described. We present three affected individuals from two families with biallelic variants (p.Met1? and p.(Asp419Asn)) in WARS1, showing varying severities of developmental delay and intellectual disability. Hearing impairment and microcephaly, as well as abnormalities of the brain, skeletal system, movement/gait, and behavior were variable features. Phenotyping of knocked down wars-1 in a Caenorhabditis elegans model showed depletion is associated with defects in germ cell development. A wars1 knockout vertebrate model recapitulates the human clinical phenotypes, confirms variant pathogenicity, and uncovers evidence implicating the p.Met1? variant as potentially impacting an exon critical for normal hearing. Together, our findings provide consolidating evidence for biallelic disruption of WARS1 as causal for an autosomal recessive neurodevelopmental syndrome and present a vertebrate model that recapitulates key phenotypes observed in patients."}],"file":[{"content_type":"application/pdf","relation":"main_file","file_id":"14370","success":1,"date_created":"2023-09-25T08:52:54Z","file_name":"2022_HumanMutation_Lin.pdf","file_size":12131312,"creator":"dernst","date_updated":"2023-09-25T08:52:54Z","access_level":"open_access","checksum":"74b01d4e4084b2f64c30ed32b18ee928"}],"issue":"10","article_processing_charge":"No","publication_identifier":{"issn":["1059-7794"]},"date_updated":"2023-09-25T08:54:14Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","scopus_import":"1","year":"2022","has_accepted_license":"1","oa_version":"Published Version","article_type":"original"},{"volume":144,"publication_status":"published","oa":1,"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1207552/","open_access":"1"}],"_id":"6161","date_published":"1996-10-01T00:00:00Z","abstract":[{"lang":"eng","text":"The tra-1 gene is a terminal regulator of somatic sex in Caenorhabditis elegans: high tra-1 activity elicits female development, low tra-1 activity elicits male development. To investigate the function and evolution of tra- 1, we examined the tra-1 gene from the closely related nematode C. briggsae. Ce-tra-1 and Cb-tra-1 are unusually divergent. Each gene generates two transcripts, but only one of these is present in both species. This common transcript encodes TRA-1A, which shows only 44% amino acid identity between the species, a figure much lower than that for previously compared genes. A Cb-tra-1 transgene rescues many tissues of tra-1(null) mutants of C. elegans but not the somatic gonad or germ line. This transgene also causes nongonadal feminization of XO animals, indicating incorrect sexual regulation. Alignment of Ce-TRA-1A and Cb-TRA-1A defined several conserved regions likely to be important for tra-1 function. The phenotype differences between Ce-tra- 1(null) mutants rescued by Cb-tra-1 transgenes and wild-type C. elegans indicate significant divergence of regulatory regions. These molecular and functional studies suggest that evolution of sex determination in nematodes is rapid and genetically complex."}],"issue":"2","external_id":{"pmid":["8889522"]},"date_updated":"2021-01-12T08:06:28Z","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","publication_identifier":{"issn":["00166731"]},"year":"1996","oa_version":"Published Version","publication":"Genetics","quality_controlled":"1","intvolume":"       144","status":"public","publisher":"Genetics Society of America","month":"10","extern":"1","date_created":"2019-03-21T11:50:37Z","page":"587-595","keyword":["amino acid sequence","article","caenorhabditis elegans","evolution","genetic variability","nonhuman","priority journal","sex determination","Amino Acid Sequence","Animals","Animals","Genetically Modified","Base Sequence","Caenorhabditis","Caenorhabditis elegans","Caenorhabditis elegans Proteins","DNA","Helminth","DNA-Binding Proteins","Evolution","Molecular","Female","Helminth Proteins","Membrane Proteins","Molecular Sequence Data","Mutagenesis","RNA","Messenger","Sequence Homology","Amino Acid","Sex Determination (Analysis)","Transcription Factors","Transgenes","Turner Syndrome","Animalia","Caenorhabditis","Caenorhabditis briggsae","Caenorhabditis elegans","Nematoda"],"language":[{"iso":"eng"}],"pmid":1,"day":"01","author":[{"last_name":"de Bono","full_name":"de Bono, Mario","first_name":"Mario","orcid":"0000-0001-8347-0443","id":"4E3FF80E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Hodgkin, J.","first_name":"J.","last_name":"Hodgkin"}],"type":"journal_article","citation":{"apa":"de Bono, M., &#38; Hodgkin, J. (1996). Evolution of sex determination in Caenorhabditis: Unusually high divergence of tra-1 and its functional consequences. <i>Genetics</i>. Genetics Society of America.","ama":"de Bono M, Hodgkin J. Evolution of sex determination in Caenorhabditis: Unusually high divergence of tra-1 and its functional consequences. <i>Genetics</i>. 1996;144(2):587-595.","short":"M. de Bono, J. Hodgkin, Genetics 144 (1996) 587–595.","mla":"de Bono, Mario, and J. Hodgkin. “Evolution of Sex Determination in Caenorhabditis: Unusually High Divergence of Tra-1 and Its Functional Consequences.” <i>Genetics</i>, vol. 144, no. 2, Genetics Society of America, 1996, pp. 587–95.","ista":"de Bono M, Hodgkin J. 1996. Evolution of sex determination in Caenorhabditis: Unusually high divergence of tra-1 and its functional consequences. Genetics. 144(2), 587–595.","ieee":"M. de Bono and J. Hodgkin, “Evolution of sex determination in Caenorhabditis: Unusually high divergence of tra-1 and its functional consequences,” <i>Genetics</i>, vol. 144, no. 2. Genetics Society of America, pp. 587–595, 1996.","chicago":"Bono, Mario de, and J. Hodgkin. “Evolution of Sex Determination in Caenorhabditis: Unusually High Divergence of Tra-1 and Its Functional Consequences.” <i>Genetics</i>. Genetics Society of America, 1996."},"title":"Evolution of sex determination in Caenorhabditis: Unusually high divergence of tra-1 and its functional consequences"}]