{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T16:04:44Z","timestamp":1780589084271,"version":"3.54.1"},"reference-count":42,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,11,14]],"date-time":"2017-11-14T00:00:00Z","timestamp":1510617600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,11,14]],"date-time":"2017-11-14T00:00:00Z","timestamp":1510617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The skeletal ciliopathies are a heterogeneous group of disorders with a significant clinical and genetic variability and the main clinical features are thoracic hypoplasia and short tubular bones. To date, 25 genes have been identified in association with skeletal ciliopathies. Mutations in the <jats:italic>KIAA0753<\/jats:italic> gene have recently been associated with Joubert syndrome\u00a0(JBTS) and orofaciodigital (OFD) syndrome. We report biallelic pathogenic variants in <jats:italic>KIAA0753<\/jats:italic> in four patients with short-rib type skeletal dysplasia. The manifestations in our patients are variable and ranging from fetal lethal to viable and moderate skeletal dysplasia with narrow thorax and abnormal metaphyses. We demonstrate that KIAA0753 is expressed in normal fetal human growth plate and show that the affected fetus, with a compound heterozygous frameshift and a nonsense mutation in <jats:italic>KIAA0753<\/jats:italic>, has an abnormal proliferative zone and a broad hypertrophic zone. The importance of <jats:italic>KIAA0753<\/jats:italic> for normal skeletal development is further confirmed by our findings that zebrafish embryos homozygous for a nonsense mutation in <jats:italic>kiaa0753<\/jats:italic> display altered cartilage patterning.<\/jats:p>","DOI":"10.1038\/s41598-017-15442-1","type":"journal-article","created":{"date-parts":[[2017,11,8]],"date-time":"2017-11-08T15:27:59Z","timestamp":1510154879000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Novel KIAA0753 mutations extend the phenotype of skeletal ciliopathies"],"prefix":"10.1038","volume":"7","author":[{"given":"A.","family":"Hammarsj\u00f6","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Vaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2907-0235","authenticated-orcid":false,"given":"F.","family":"Taylan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Sedghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. M.","family":"Girisha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Chitayat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Neethukrishna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Shannon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Godoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Gowrishankar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Lindstrand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Nasiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Baktashian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. T.","family":"Newton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W.","family":"Hofmeister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Pettersson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2696-5850","authenticated-orcid":false,"given":"A. S.","family":"Chagin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Nishimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Matsumoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Nordgren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Miyake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Grigelioniene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Ikegawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,11,14]]},"reference":[{"key":"15442_CR1","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1038\/nrm2278","volume":"8","author":"M Fliegauf","year":"2007","unstructured":"Fliegauf, M., Benzing, T. & Omran, H. When cilia go bad: cilia defects and ciliopathies. Nat Rev Mol Cell Biol \n                           8, 880\u2013893, https:\/\/doi.org\/10.1038\/nrm2278 (2007).","journal-title":"Nat Rev Mol Cell Biol"},{"key":"15442_CR2","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1038\/nrm.2017.60","volume":"18","author":"JF Reiter","year":"2017","unstructured":"Reiter, J. F. & Leroux, M. R. Genes and molecular pathways underpinning ciliopathies. Nat Rev Mol Cell Biol \n                           18, 533\u2013547, https:\/\/doi.org\/10.1038\/nrm.2017.60 (2017).","journal-title":"Nat Rev Mol Cell Biol"},{"key":"15442_CR3","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37365","author":"L Bonafe","year":"2015","unstructured":"Bonafe, L. et al. Nosology and classification of genetic skeletal disorders: 2015 revision. American journal of medical genetics. Part A. https:\/\/doi.org\/10.1002\/ajmg.a.37365 (2015).","journal-title":"American journal of medical genetics. Part A"},{"key":"15442_CR4","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1002\/path.4843","volume":"241","author":"HM Mitchison","year":"2017","unstructured":"Mitchison, H. M. & Valente, E. M. Motile and non-motile cilia in human pathology: from function to phenotypes. J Pathol \n                           241, 294\u2013309, https:\/\/doi.org\/10.1002\/path.4843 (2017).","journal-title":"J Pathol"},{"key":"15442_CR5","doi-asserted-by":"publisher","DOI":"10.1038\/srep34232","volume":"6","author":"I Duran","year":"2016","unstructured":"Duran, I. et al. Destabilization of the IFT-B cilia core complex due to mutations in IFT81 causes a Spectrum of Short-Rib Polydactyly Syndrome. Sci Rep \n                           6, 34232, https:\/\/doi.org\/10.1038\/srep34232 (2016).","journal-title":"Sci Rep"},{"key":"15442_CR6","doi-asserted-by":"publisher","DOI":"10.1038\/srep24083","volume":"6","author":"CR Cortes","year":"2016","unstructured":"Cortes, C. R. et al. Mutations in human C2CD3 cause skeletal dysplasia and provide new insights into phenotypic and cellular consequences of altered C2CD3 function. Sci Rep \n                           6, 24083, https:\/\/doi.org\/10.1038\/srep24083 (2016).","journal-title":"Sci Rep"},{"key":"15442_CR7","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.ajhg.2013.11.019","volume":"94","author":"K Tuz","year":"2014","unstructured":"Tuz, K. et al. Mutations in CSPP1 cause primary cilia abnormalities and Joubert syndrome with or without Jeune asphyxiating thoracic dystrophy. American journal of human genetics \n                           94, 62\u201372, https:\/\/doi.org\/10.1016\/j.ajhg.2013.11.019 (2014).","journal-title":"American journal of human genetics"},{"key":"15442_CR8","doi-asserted-by":"publisher","first-page":"1824","DOI":"10.1093\/hmg\/ddw054","volume":"25","author":"JP Casey","year":"2016","unstructured":"Casey, J. P. et al. Recessive NEK9 mutation causes a lethal skeletal dysplasia with evidence of cell cycle and ciliary defects. Human molecular genetics \n                           25, 1824\u20131835, https:\/\/doi.org\/10.1093\/hmg\/ddw054 (2016).","journal-title":"Human molecular genetics"},{"key":"15442_CR9","doi-asserted-by":"publisher","first-page":"1698","DOI":"10.1002\/ajmg.a.38215","volume":"173","author":"AM McInerney-Leo","year":"2017","unstructured":"McInerney-Leo, A. M. et al. Homozygous variant in C21orf2 in a case of Jeune syndrome with severe thoracic involvement: Extending the phenotypic spectrum. American journal of medical genetics. Part A \n                           173, 1698\u20131704, https:\/\/doi.org\/10.1002\/ajmg.a.38215 (2017).","journal-title":"American journal of medical genetics. Part A"},{"key":"15442_CR10","doi-asserted-by":"publisher","first-page":"1411","DOI":"10.1002\/ajmg.a.33416","volume":"152A","author":"AM Lehman","year":"2010","unstructured":"Lehman, A. M. et al. Co-occurrence of Joubert syndrome and Jeune asphyxiating thoracic dystrophy. American journal of medical genetics. Part A \n                           152A, 1411\u20131419, https:\/\/doi.org\/10.1002\/ajmg.a.33416 (2010).","journal-title":"American journal of medical genetics. Part A"},{"key":"15442_CR11","doi-asserted-by":"publisher","first-page":"1520","DOI":"10.1038\/emboj.2011.63","volume":"30","author":"L Jakobsen","year":"2011","unstructured":"Jakobsen, L. et al. Novel asymmetrically localizing components of human centrosomes identified by complementary proteomics methods. EMBO J \n                           30, 1520\u20131535, https:\/\/doi.org\/10.1038\/emboj.2011.63 (2011).","journal-title":"EMBO J"},{"key":"15442_CR12","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1093\/hmg\/ddv488","volume":"25","author":"V Chevrier","year":"2016","unstructured":"Chevrier, V. et al. OFIP\/KIAA0753 forms a complex with OFD1 and FOR20 at pericentriolar satellites and centrosomes and is mutated in one individual with oral-facial-digital syndrome. Human molecular genetics \n                           25, 497\u2013513, https:\/\/doi.org\/10.1093\/hmg\/ddv488 (2016).","journal-title":"Human molecular genetics"},{"key":"15442_CR13","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1016\/j.cub.2014.01.067","volume":"24","author":"EN Firat-Karalar","year":"2014","unstructured":"Firat-Karalar, E. N., Rauniyar, N., Yates, J. R. 3rd & Stearns, T. Proximity interactions among centrosome components identify regulators of centriole duplication. Curr Biol \n                           24, 664\u2013670, https:\/\/doi.org\/10.1016\/j.cub.2014.01.067 (2014).","journal-title":"Curr Biol"},{"key":"15442_CR14","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1007\/s00439-017-1765-z","volume":"136","author":"J Stephen","year":"2017","unstructured":"Stephen, J. et al. Mutations in KIAA0753 cause Joubert syndrome associated with growth hormone deficiency. Hum Genet \n                           136, 399\u2013408, https:\/\/doi.org\/10.1007\/s00439-017-1765-z (2017).","journal-title":"Hum Genet"},{"key":"15442_CR15","doi-asserted-by":"publisher","first-page":"4085","DOI":"10.1242\/dev.01240","volume":"131","author":"Z Sun","year":"2004","unstructured":"Sun, Z. et al. A genetic screen in zebrafish identifies cilia genes as a principal cause of cystic kidney. Development \n                           131, 4085\u20134093, https:\/\/doi.org\/10.1242\/dev.01240 (2004).","journal-title":"Development"},{"key":"15442_CR16","doi-asserted-by":"publisher","first-page":"2529","DOI":"10.1002\/ajmg.a.36669","volume":"164A","author":"T Mitsui","year":"2014","unstructured":"Mitsui, T. et al. Acroscyphodysplasia as a phenotypic variation of pseudohypoparathyroidism and acrodysostosis type 2. American journal of medical genetics. Part A \n                           164A, 2529\u20132534, https:\/\/doi.org\/10.1002\/ajmg.a.36669 (2014).","journal-title":"American journal of medical genetics. Part A"},{"key":"15442_CR17","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1111\/j.1399-0004.1991.tb03043.x","volume":"39","author":"A Verloes","year":"1991","unstructured":"Verloes, A., Le Merrer, M., Farriaux, J. P. & Maroteaux, P. Metaphyseal acroscyphodysplasia. Clinical genetics \n                           39, 362\u2013369 (1991).","journal-title":"Clinical genetics"},{"key":"15442_CR18","doi-asserted-by":"publisher","first-page":"608","DOI":"10.1136\/jmedgenet-2016-103832","volume":"53","author":"S Roosing","year":"2016","unstructured":"Roosing, S. et al. Mutations in CEP120 cause Joubert syndrome as well as complex ciliopathy phenotypes. Journal of medical genetics \n                           53, 608\u2013615, https:\/\/doi.org\/10.1136\/jmedgenet-2016-103832 (2016).","journal-title":"Journal of medical genetics"},{"key":"15442_CR19","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1093\/hmg\/ddu555","volume":"24","author":"R Shaheen","year":"2015","unstructured":"Shaheen, R. et al. A founder CEP120 mutation in Jeune asphyxiating thoracic dystrophy expands the role of centriolar proteins in skeletal ciliopathies. Human molecular genetics \n                           24, 1410\u20131419, https:\/\/doi.org\/10.1093\/hmg\/ddu555 (2015).","journal-title":"Human molecular genetics"},{"key":"15442_CR20","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1146\/annurev-genet-111212-133424","volume":"47","author":"MW Popp","year":"2013","unstructured":"Popp, M. W. & Maquat, L. E. Organizing principles of mammalian nonsense-mediated mRNA decay. Annu Rev Genet \n                           47, 139\u2013165, https:\/\/doi.org\/10.1146\/annurev-genet-111212-133424 (2013).","journal-title":"Annu Rev Genet"},{"key":"15442_CR21","doi-asserted-by":"publisher","first-page":"3238","DOI":"10.1093\/brain\/awv263","volume":"138","author":"K Hardies","year":"2015","unstructured":"Hardies, K. et al. Recessive mutations in SLC13A5 result in a loss of citrate transport and cause neonatal epilepsy, developmental delay and teeth hypoplasia. Brain \n                           138, 3238\u20133250, https:\/\/doi.org\/10.1093\/brain\/awv263 (2015).","journal-title":"Brain"},{"key":"15442_CR22","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1136\/jmedgenet-2016-103988","volume":"54","author":"A Schossig","year":"2017","unstructured":"Schossig, A. et al. SLC13A5 is the second gene associated with Kohlschutter-Tonz syndrome. Journal of medical genetics \n                           54, 54\u201362, https:\/\/doi.org\/10.1136\/jmedgenet-2016-103988 (2017).","journal-title":"Journal of medical genetics"},{"key":"15442_CR23","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1056\/NEJMoa1516767","volume":"376","author":"JE Posey","year":"2017","unstructured":"Posey, J. E. et al. Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation. N Engl J Med \n                           376, 21\u201331, https:\/\/doi.org\/10.1056\/NEJMoa1516767 (2017).","journal-title":"N Engl J Med"},{"key":"15442_CR24","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12987","author":"TB Balci","year":"2017","unstructured":"Balci, T. B. et al. Debunking Occam\u2019s razor: Diagnosing multiple genetic diseases in families by whole-exome sequencing. Clinical genetics. https:\/\/doi.org\/10.1111\/cge.12987 (2017).","journal-title":"Clinical genetics"},{"key":"15442_CR25","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.ydbio.2007.02.003","volume":"305","author":"B Song","year":"2007","unstructured":"Song, B., Haycraft, C. J., Seo, H. S., Yoder, B. K. & Serra, R. Development of the post-natal growth plate requires intraflagellar transport proteins. Dev Biol \n                           305, 202\u2013216, https:\/\/doi.org\/10.1016\/j.ydbio.2007.02.003 (2007).","journal-title":"Dev Biol"},{"key":"15442_CR26","doi-asserted-by":"publisher","first-page":"e0130618","DOI":"10.1371\/journal.pone.0130618","volume":"10","author":"X Yuan","year":"2015","unstructured":"Yuan, X. & Yang, S. Deletion of IFT80 Impairs Epiphyseal and Articular Cartilage Formation Due to Disruption of Chondrocyte Differentiation. PloS one \n                           10, e0130618, https:\/\/doi.org\/10.1371\/journal.pone.0130618 (2015).","journal-title":"PloS one"},{"key":"15442_CR27","doi-asserted-by":"publisher","first-page":"1306","DOI":"10.1093\/hmg\/ddr013","volume":"20","author":"S Rix","year":"2011","unstructured":"Rix, S., Calmont, A., Scambler, P. J. & Beales, P. L. An Ift80 mouse model of short rib polydactyly syndromes shows defects in hedgehog signalling without loss or malformation of cilia. Human molecular genetics \n                           20, 1306\u20131314, https:\/\/doi.org\/10.1093\/hmg\/ddr013 (2011).","journal-title":"Human molecular genetics"},{"key":"15442_CR28","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1093\/hmg\/ddn384","volume":"18","author":"LM DiBella","year":"2009","unstructured":"DiBella, L. M., Park, A. & Sun, Z. Zebrafish Tsc1 reveals functional interactions between the cilium and the TOR pathway. Human molecular genetics \n                           18, 595\u2013606, https:\/\/doi.org\/10.1093\/hmg\/ddn384 (2009).","journal-title":"Human molecular genetics"},{"key":"15442_CR29","doi-asserted-by":"publisher","first-page":"e27365","DOI":"10.1371\/journal.pone.0027365","volume":"6","author":"J Li","year":"2011","unstructured":"Li, J. & Sun, Z. Qilin is essential for cilia assembly and normal kidney development in zebrafish. PloS one \n                           6, e27365, https:\/\/doi.org\/10.1371\/journal.pone.0027365 (2011).","journal-title":"PloS one"},{"key":"15442_CR30","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.ydbio.2015.02.009","volume":"400","author":"MS Lee","year":"2015","unstructured":"Lee, M. S. et al. IFT46 plays an essential role in cilia development. Dev Biol \n                           400, 248\u2013257, https:\/\/doi.org\/10.1016\/j.ydbio.2015.02.009 (2015).","journal-title":"Dev Biol"},{"key":"15442_CR31","doi-asserted-by":"publisher","first-page":"1907","DOI":"10.1242\/dev.01772","volume":"132","author":"AG Kramer-Zucker","year":"2005","unstructured":"Kramer-Zucker, A. G. et al. Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer\u2019s vesicle is required for normal organogenesis. Development \n                           132, 1907\u20131921, https:\/\/doi.org\/10.1242\/dev.01772 (2005).","journal-title":"Development"},{"key":"15442_CR32","doi-asserted-by":"publisher","first-page":"1316","DOI":"10.1038\/ng1892","volume":"38","author":"I Oishi","year":"2006","unstructured":"Oishi, I., Kawakami, Y., Raya, A., Callol-Massot, C. & Izpisua Belmonte, J. C. Regulation of primary cilia formation and left-right patterning in zebrafish by a noncanonical Wnt signaling mediator, duboraya. Nature genetics \n                           38, 1316\u20131322, https:\/\/doi.org\/10.1038\/ng1892 (2006).","journal-title":"Nature genetics"},{"key":"15442_CR33","doi-asserted-by":"publisher","first-page":"2807","DOI":"10.1242\/dev.022228","volume":"135","author":"P Oteiza","year":"2008","unstructured":"Oteiza, P., Koppen, M., Concha, M. L. & Heisenberg, C. P. Origin and shaping of the laterality organ in zebrafish. Development \n                           135, 2807\u20132813, https:\/\/doi.org\/10.1242\/dev.022228 (2008).","journal-title":"Development"},{"key":"15442_CR34","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1038\/jhg.2016.157","volume":"62","author":"Z Wang","year":"2017","unstructured":"Wang, Z. et al. Axial spondylometaphyseal dysplasia is also caused by NEK1 mutations. J Hum Genet \n                           62, 503\u2013506, https:\/\/doi.org\/10.1038\/jhg.2016.157 (2017).","journal-title":"J Hum Genet"},{"key":"15442_CR35","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.tjog.2012.01.020","volume":"51","author":"CP Chen","year":"2012","unstructured":"Chen, C. P. et al. Short rib-polydactyly syndrome type II (Majewski): prenatal diagnosis, perinatal imaging findings and molecular analysis of the NEK1gene. Taiwanese journal of obstetrics & gynecology \n                           51, 100\u2013105, https:\/\/doi.org\/10.1016\/j.tjog.2012.01.020 (2012).","journal-title":"Taiwanese journal of obstetrics & gynecology"},{"key":"15442_CR36","doi-asserted-by":"publisher","first-page":"e90581","DOI":"10.1371\/journal.pone.0090581","volume":"9","author":"WP Lee","year":"2014","unstructured":"Lee, W. P. et al. MOSAIK: a hash-based algorithm for accurate next-generation sequencing short-read mapping. PloS one \n                           9, e90581, https:\/\/doi.org\/10.1371\/journal.pone.0090581 (2014).","journal-title":"PloS one"},{"key":"15442_CR37","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","volume":"20","author":"A McKenna","year":"2010","unstructured":"McKenna, A. et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res \n                           20, 1297\u20131303, https:\/\/doi.org\/10.1101\/gr.107524.110 (2010).","journal-title":"Genome Res"},{"key":"15442_CR38","doi-asserted-by":"publisher","first-page":"e164","DOI":"10.1093\/nar\/gkq603","volume":"38","author":"K Wang","year":"2010","unstructured":"Wang, K., Li, M. & Hakonarson, H. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res \n                           38, e164, https:\/\/doi.org\/10.1093\/nar\/gkq603 (2010).","journal-title":"Nucleic Acids Res"},{"key":"15442_CR39","doi-asserted-by":"publisher","first-page":"2069","DOI":"10.1093\/bioinformatics\/btq330","volume":"26","author":"W McLaren","year":"2010","unstructured":"McLaren, W. et al. Deriving the consequences of genomic variants with the Ensembl API and SNP Effect Predictor. Bioinformatics (Oxford, England) \n                           26, 2069\u20132070, https:\/\/doi.org\/10.1093\/bioinformatics\/btq330 (2010).","journal-title":"Bioinformatics (Oxford, England)"},{"key":"15442_CR40","doi-asserted-by":"publisher","first-page":"e1003153","DOI":"10.1371\/journal.pcbi.1003153","volume":"9","author":"U Paila","year":"2013","unstructured":"Paila, U., Chapman, B. A., Kirchner, R. & Quinlan, A. R. GEMINI: integrative exploration of genetic variation and genome annotations. PLoS Comput Biol \n                           9, e1003153, https:\/\/doi.org\/10.1371\/journal.pcbi.1003153 (2013).","journal-title":"PLoS Comput Biol"},{"key":"15442_CR41","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1038\/ng.2892","volume":"46","author":"M Kircher","year":"2014","unstructured":"Kircher, M. et al. A general framework for estimating the relative pathogenicity of human genetic variants. Nature genetics \n                           46, 310\u2013315, https:\/\/doi.org\/10.1038\/ng.2892 (2014).","journal-title":"Nature genetics"},{"key":"15442_CR42","doi-asserted-by":"publisher","DOI":"10.1038\/jhg.2017.35","author":"A Shukla","year":"2017","unstructured":"Shukla, A. et al. Homozygous p.(Glu87Lys) variant in ISCA1 is associated with a multiple mitochondrial dysfunctions syndrome. J Hum Genet. https:\/\/doi.org\/10.1038\/jhg.2017.35 (2017).","journal-title":"J Hum Genet"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-15442-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-15442-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-15442-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T13:34:38Z","timestamp":1671802478000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-15442-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,14]]},"references-count":42,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["15442"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-15442-1","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,14]]},"assertion":[{"value":"18 July 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 October 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 November 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"15585"}}