{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T15:39:38Z","timestamp":1780760378021,"version":"3.54.1"},"reference-count":68,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T00:00:00Z","timestamp":1613433600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T00:00:00Z","timestamp":1613433600000},"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":["npj Genom. Med."],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Collectively, rare genetic diseases affect a significant number of individuals worldwide. In this study, we have conducted whole-exome sequencing (WES) and identified underlying pathogenic or likely pathogenic variants in five children with rare genetic diseases. We present evidence for disease-causing autosomal recessive variants in a range of disease-associated genes such as <jats:italic>DHH<\/jats:italic>-associated 46,XY gonadal dysgenesis (GD) or 46,XY sex reversal 7, <jats:italic>GNPTAB<\/jats:italic>-associated mucolipidosis II alpha\/beta (ML II), <jats:italic>BBS1<\/jats:italic>-associated Bardet\u2013Biedl Syndrome (BBS), <jats:italic>SURF1<\/jats:italic>-associated Leigh Syndrome (LS) and <jats:italic>AP4B1<\/jats:italic>-associated spastic paraplegia-47 (SPG47) in unrelated affected members from Bangladesh. Our analysis pipeline detected three homozygous mutations, including a novel c. 863\u2009G\u2009&gt;\u2009C (p.Pro288Arg) variant in <jats:italic>DHH<\/jats:italic>, and two compound heterozygous variants, including two novel variants: c.2972dupT (p.Met991Ilefs*) in <jats:italic>GNPTAB<\/jats:italic> and c.229\u2009G\u2009&gt;\u2009C (p.Gly77Arg) in <jats:italic>SURF1<\/jats:italic>. All mutations were validated by Sanger sequencing. Collectively, this study adds to the genetic heterogeneity of rare genetic diseases and is the first report elucidating the genetic profile of (consanguineous and nonconsanguineous) rare genetic diseases in the Bangladesh population.<\/jats:p>","DOI":"10.1038\/s41525-021-00173-0","type":"journal-article","created":{"date-parts":[[2021,2,17]],"date-time":"2021-02-17T18:37:58Z","timestamp":1613587078000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Whole exome sequencing uncovered highly penetrant recessive mutations for a spectrum of rare genetic pediatric diseases in Bangladesh"],"prefix":"10.1038","volume":"6","author":[{"given":"Hosneara","family":"Akter","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Shahnoor","family":"Hossain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nushrat Jahan","family":"Dity","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md. Atikur","family":"Rahaman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. M.","family":"Furkan Uddin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8883-9630","authenticated-orcid":false,"given":"Nasna","family":"Nassir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghausia","family":"Begum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reem Abdel","family":"Hameid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5424-6194","authenticated-orcid":false,"given":"Muhammad Sougatul","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahrima Arman","family":"Tusty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Basiruzzaman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoli","family":"Sarkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazharul","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharmin","family":"Jahan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3651-0654","authenticated-orcid":false,"given":"Elaine T.","family":"Lim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Woodbury-Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitri James","family":"Stavropoulos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren D.","family":"O\u2019Rielly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bakhrom K.","family":"Berdeiv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. H. M.","family":"Nurun Nabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Nazmul","family":"Ahsan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8326-1999","authenticated-orcid":false,"given":"Stephen W.","family":"Scherer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Uddin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,16]]},"reference":[{"key":"173_CR1","first-page":"677","volume":"42","author":"PA Baird","year":"1988","unstructured":"Baird, P. A., Anderson, T. W., Newcombe, H. B. & Lowry, R. B. Genetic disorders in children and young adults: a population study. Am. J. Hum. Genet. 42, 677 (1988).","journal-title":"Am. J. Hum. Genet."},{"key":"173_CR2","doi-asserted-by":"publisher","first-page":"1426","DOI":"10.1002\/ccr3.1595","volume":"6","author":"KF Uddin","year":"2018","unstructured":"Uddin, K. F. et al. An ANKRD26 nonsense somatic mutation in a female with epidermodysplasia verruciformis (Tree Man Syndrome). Clin. case Rep. 6, 1426 (2018).","journal-title":"Clin. case Rep."},{"key":"173_CR3","doi-asserted-by":"crossref","unstructured":"Guedenon, K. M. et al. Hutchinson\u2010Gilford Progeria syndrome: report of the first Togolese case. Am. J. Med. Genet. Part A 182, 1316\u20131320 (2020).","DOI":"10.1002\/ajmg.a.61581"},{"key":"173_CR4","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-019-0881-0","volume":"20","author":"H Akter","year":"2019","unstructured":"Akter, H. et al. Novel mutations in actionable breast cancer genes by targeted sequencing in an ethnically homogenous cohort. BMC Med. Genet. 20, 150 (2019).","journal-title":"BMC Med. Genet."},{"key":"173_CR5","volume":"7","author":"MM Rahman","year":"2019","unstructured":"Rahman, M. M. et al. Gonadal mosaicism of large terminal de novo duplication and deletion in siblings with variable intellectual disability phenotypes. Mol. Genet. Genom. Med. 7, e00954 (2019).","journal-title":"Mol. Genet. Genom. Med."},{"key":"173_CR6","first-page":"2981","volume":"12","author":"F Yu","year":"2019","unstructured":"Yu, F. et al. Compound heterozygous GNPTAB mutations cause mucolipidosis II or III alpha\/beta in two Chinese families. Int. J. Clin. Exp. Pathol. 12, 2981 (2019).","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"173_CR7","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1007\/s42000-019-00116-6","volume":"18","author":"V Neocleous","year":"2019","unstructured":"Neocleous, V. et al. 46, XY complete gonadal dysgenesis in a familial case with a rare mutation in the desert hedgehog (DHH) gene. Hormones 18, 315\u2013320 (2019).","journal-title":"Hormones"},{"key":"173_CR8","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1038\/ng.2980","volume":"46","author":"M Uddin","year":"2014","unstructured":"Uddin, M. et al. Brain-expressed exons under purifying selection are enriched for de novo mutations in autism spectrum disorder. Nat. Genet. 46, 742 (2014).","journal-title":"Nat. Genet."},{"key":"173_CR9","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1001\/jama.2015.10078","volume":"314","author":"K Tammimies","year":"2015","unstructured":"Tammimies, K. et al. Molecular diagnostic yield of chromosomal microarray analysis and whole-exome sequencing in children with autism spectrum disorder. Jama 314, 895\u2013903 (2015).","journal-title":"Jama"},{"key":"173_CR10","doi-asserted-by":"publisher","unstructured":"Rahaman, M. A. et al. An exploration of physical and phenotypic characteristics of Bangladeshi children with autism spectrum disorder. J. Autism Dev. Disorders https:\/\/doi.org\/10.1007\/s10803-020-04703-0 (2020).","DOI":"10.1007\/s10803-020-04703-0"},{"key":"173_CR11","first-page":"7.20. 21","volume":"76","author":"I Adzhubei","year":"2013","unstructured":"Adzhubei, I., Jordan, D. M. & Sunyaev, S. R. Predicting functional effect of human missense mutations using PolyPhen\u20102. Curr. Protoc. Hum. Genet. 76, 7.20. 21\u201327.20. 41 (2013).","journal-title":"Curr. Protoc. Hum. Genet."},{"key":"173_CR12","doi-asserted-by":"publisher","first-page":"D886","DOI":"10.1093\/nar\/gky1016","volume":"47","author":"P Rentzsch","year":"2019","unstructured":"Rentzsch, P., Witten, D., Cooper, G. M., Shendure, J. & Kircher, M. CADD: predicting the deleteriousness of variants throughout the human genome. Nucleic acids Res. 47, D886\u2013D894 (2019).","journal-title":"Nucleic acids Res."},{"key":"173_CR13","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards, S. et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 17, 405\u2013423 (2015).","journal-title":"Genet. Med."},{"key":"173_CR14","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1111\/j.1399-0004.2010.01539.x","volume":"80","author":"MF Coutinho","year":"2011","unstructured":"Coutinho, M. F. et al. Origin and spread of a common deletion causing mucolipidosis type II: insights from patterns of haplotypic diversity. Clin. Genet. 80, 273\u2013280 (2011).","journal-title":"Clin. Genet."},{"key":"173_CR15","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1136\/jmg.2009.067736","volume":"47","author":"SS Cathey","year":"2010","unstructured":"Cathey, S. S. et al. Phenotype and genotype in mucolipidoses II and III alpha\/beta: a study of 61 probands. J. Med. Genet. 47, 38\u201348 (2010).","journal-title":"J. Med. Genet."},{"key":"173_CR16","doi-asserted-by":"publisher","first-page":"E956","DOI":"10.1002\/humu.21099","volume":"30","author":"B Tappino","year":"2009","unstructured":"Tappino, B. et al. Molecular characterization of 22 novel UDP\u2010N\u2010acetylglucosamine\u20101\u2010phosphate transferase \u03b1\u2010and \u03b2\u2010subunit (GNPTAB) gene mutations causing mucolipidosis types II\u03b1\/\u03b2 and III\u03b1\/\u03b2 in 46 patients. Hum. Mutat. 30, E956\u2013E973 (2009).","journal-title":"Hum. Mutat."},{"key":"173_CR17","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1002\/humu.22502","volume":"35","author":"R De Pace","year":"2014","unstructured":"De Pace, R. et al. Mucolipidosis II\u2010related mutations inhibit the exit from the endoplasmic reticulum and proteolytic cleavage of G lc NA c\u20101\u2010phosphotransferase precursor protein (GNPTAB). Hum. Mutat. 35, 368\u2013376 (2014).","journal-title":"Hum. Mutat."},{"key":"173_CR18","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1136\/jmg.36.6.437","volume":"36","author":"P Beales","year":"1999","unstructured":"Beales, P., Elcioglu, N., Woolf, A., Parker, D. & Flinter, F. New criteria for improved diagnosis of Bardet-Biedl syndrome: results of a population survey. J. Med. Genet. 36, 437\u2013446 (1999).","journal-title":"J. Med. Genet."},{"key":"173_CR19","unstructured":"Mugundhan, K., Thiruvarutchlvan, K. & Sivakumar, S. Bardet-Biedl syndrome with seizures\u2013a rare association. J. Assoc. Physician India 61, 484 (2013)."},{"key":"173_CR20","doi-asserted-by":"publisher","first-page":"10","DOI":"10.4103\/0971-4065.35014","volume":"17","author":"M Rathi","year":"2007","unstructured":"Rathi, M. et al. Bardet-Biedl syndrome with end-stage kidney disease: a case report and review of literature. Indian J. Nephrol. 17, 10 (2007).","journal-title":"Indian J. Nephrol."},{"key":"173_CR21","doi-asserted-by":"publisher","first-page":"4250","DOI":"10.1093\/nar\/gkm402","volume":"35","author":"E Buratti","year":"2007","unstructured":"Buratti, E. et al. Aberrant 5\u2032 splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. Nucleic acids Res. 35, 4250\u20134263 (2007).","journal-title":"Nucleic acids Res."},{"key":"173_CR22","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-8-96","volume":"8","author":"Y Wedatilake","year":"2013","unstructured":"Wedatilake, Y. et al. SURF1 deficiency: a multi-centre natural history study. Orphanet J. rare Dis. 8, 96 (2013).","journal-title":"Orphanet J. rare Dis."},{"key":"173_CR23","doi-asserted-by":"publisher","first-page":"110","DOI":"10.2478\/enr-2018-0013","volume":"52","author":"D Danis","year":"2018","unstructured":"Danis, D. et al. Mutations in SURF1 are important genetic causes of Leigh syndrome in Slovak patients. Endocr. Regul. 52, 110\u2013118 (2018).","journal-title":"Endocr. Regul."},{"key":"173_CR24","doi-asserted-by":"publisher","first-page":"3812","DOI":"10.1093\/nar\/gkg509","volume":"31","author":"PC Ng","year":"2003","unstructured":"Ng, P. C. & Henikoff, S. SIFT: Predicting amino acid changes that affect protein function. Nucleic acids Res. 31, 3812\u20133814 (2003).","journal-title":"Nucleic acids Res."},{"key":"173_CR25","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1007\/s004399900191","volume":"105","author":"M Teraoka","year":"1999","unstructured":"Teraoka, M. et al. Two novel mutations of SURF1 in Leigh syndrome with cytochrome c oxidase deficiency. Hum. Genet. 105, 560\u2013563 (1999).","journal-title":"Hum. Genet."},{"key":"173_CR26","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.mito.2015.08.002","volume":"25","author":"PS Bindu","year":"2015","unstructured":"Bindu, P. S. et al. Magnetic resonance imaging correlates of genetically characterized patients with mitochondrial disorders: a study from south India. Mitochondrion 25, 6\u201316 (2015).","journal-title":"Mitochondrion"},{"key":"173_CR27","doi-asserted-by":"publisher","first-page":"D862","DOI":"10.1093\/nar\/gkv1222","volume":"44","author":"MJ Landrum","year":"2016","unstructured":"Landrum, M. J. et al. ClinVar: public archive of interpretations of clinically relevant variants. Nucleic acids Res. 44, D862\u2013D868 (2016).","journal-title":"Nucleic acids Res."},{"key":"173_CR28","doi-asserted-by":"publisher","first-page":"7278","DOI":"10.1074\/jbc.274.11.7278","volume":"274","author":"EC Dell\u2019Angelica","year":"1999","unstructured":"Dell\u2019Angelica, E. C., Mullins, C. & Bonifacino, J. S. AP-4, a novel protein complex related to clathrin adaptors. J. Biol. Chem. 274, 7278\u20137285 (1999).","journal-title":"J. Biol. Chem."},{"key":"173_CR29","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/s10048-012-0314-0","volume":"13","author":"P Bauer","year":"2012","unstructured":"Bauer, P. et al. Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47). Neurogenetics 13, 73\u201376 (2012).","journal-title":"Neurogenetics"},{"key":"173_CR30","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1038\/ejhg.2014.73","volume":"23","author":"H Abdollahpour","year":"2015","unstructured":"Abdollahpour, H. et al. An AP4B1 frameshift mutation in siblings with intellectual disability and spastic tetraplegia further delineates the AP-4 deficiency syndrome. Eur. J. Hum. Genet. 23, 256\u2013259 (2015).","journal-title":"Eur. J. Hum. Genet."},{"key":"173_CR31","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1002\/ajmg.a.38561","volume":"176","author":"D Ebrahimi\u2010Fakhari","year":"2018","unstructured":"Ebrahimi\u2010Fakhari, D. et al. Clinical and genetic characterization of AP4B1\u2010associated SPG47. Am. J. Med. Genet. Part A 176, 311\u2013318 (2018).","journal-title":"Am. J. Med. Genet. Part A"},{"key":"173_CR32","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1159\/000015495","volume":"88","author":"G Tate","year":"2000","unstructured":"Tate, G., Satoh, H., Endo, Y. & Mitsuya, T. Assignment1 of Desert Hedgehog (DHH) to human chromosome bands 12q12\u2192 q13. 1 by in situ hybridization. Cytogenetic Genome Res. 88, 93\u201394 (2000).","journal-title":"Cytogenetic Genome Res."},{"key":"173_CR33","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1038\/nrg2984","volume":"12","author":"PW Ingham","year":"2011","unstructured":"Ingham, P. W., Nakano, Y. & Seger, C. Mechanisms and functions of Hedgehog signalling across the metazoa. Nat. Rev. Genet. 12, 393\u2013406 (2011).","journal-title":"Nat. Rev. Genet."},{"key":"173_CR34","doi-asserted-by":"crossref","unstructured":"Sasai, N., Toriyama, M. & Kondo, T. Hedgehog signal and genetic disorders. Front. Genet. 10, 1103 (2019).","DOI":"10.3389\/fgene.2019.01103"},{"key":"173_CR35","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1242\/dev.120154","volume":"143","author":"RTH Lee","year":"2016","unstructured":"Lee, R. T. H., Zhao, Z. & Ingham, P. W. Hedgehog signalling. Development 143, 367\u2013372 (2016).","journal-title":"Development"},{"key":"173_CR36","doi-asserted-by":"crossref","unstructured":"Petrov, K., Wierbowski, B. M. & Salic, A. Sending and receiving hedgehog signals. Ann. Rev. Cell Dev. Biol. 33, 145\u2013168 (2017).","DOI":"10.1146\/annurev-cellbio-100616-060847"},{"key":"173_CR37","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1093\/molehr\/gah216","volume":"11","author":"P Canto","year":"2005","unstructured":"Canto, P., Vilchis, F., S\u00f6derlund, D., Reyes, E. & Mendez, J. A heterozygous mutation in the desert hedgehog gene in patients with mixed gonadal dysgenesis. Mol. Hum. Reprod. 11, 833\u2013836 (2005).","journal-title":"Mol. Hum. Reprod."},{"key":"173_CR38","doi-asserted-by":"publisher","first-page":"4480","DOI":"10.1210\/jc.2004-0863","volume":"89","author":"P Canto","year":"2004","unstructured":"Canto, P., S\u00f6derlund, D., Reyes, E. & Mendez, J. Mutations in the desert hedgehog (DHH) gene in patients with 46. XY Complet. pure gonadal dysgenesis. J. Clin. Endocrinol. Metab. 89, 4480\u20134483 (2004).","journal-title":"XY Complet. pure gonadal dysgenesis. J. Clin. Endocrinol. Metab."},{"key":"173_CR39","doi-asserted-by":"publisher","first-page":"E1022","DOI":"10.1210\/jc.2015-1314","volume":"100","author":"R Werner","year":"2015","unstructured":"Werner, R. et al. 46, XY gonadal dysgenesis due to a homozygous mutation in desert hedgehog (DHH) identified by exome sequencing. J. Clin. Endocrinol. Metab. 100, E1022\u2013E1029 (2015).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"173_CR40","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1159\/000485507","volume":"89","author":"F Baldinotti","year":"2018","unstructured":"Baldinotti, F. et al. Novel familial variant of the desert hedgehog gene: clinical findings in two Sisters with 46, XY gonadal dysgenesis or 46, XX karyotype and literature review. Horm. Res. Paediatrics 89, 141\u2013149 (2018).","journal-title":"Horm. Res. Paediatrics"},{"key":"173_CR41","doi-asserted-by":"publisher","first-page":"2097","DOI":"10.1002\/humu.23664","volume":"39","author":"A Tajouri","year":"2018","unstructured":"Tajouri, A. et al. In vitro functional characterization of the novel DHH mutations p.(Asn337Lysfs* 24) and p.(Glu212Lys) associated with gonadal dysgenesis. Hum. Mutat. 39, 2097\u20132109 (2018).","journal-title":"Hum. Mutat."},{"key":"173_CR42","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1086\/321210","volume":"67","author":"F Umehara","year":"2000","unstructured":"Umehara, F. et al. A novel mutation of desert hedgehog in a patient with 46, XY partial gonadal dysgenesis accompanied by minifascicular neuropathy. Am. J. Hum. Genet. 67, 1302\u20131305 (2000).","journal-title":"Am. J. Hum. Genet."},{"key":"173_CR43","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1086\/500849","volume":"78","author":"M Kudo","year":"2006","unstructured":"Kudo, M., Brem, M. S. & Canfield, W. M. Mucolipidosis II (I-cell disease) and mucolipidosis IIIA (classical pseudo-Hurler polydystrophy) are caused by mutations in the GlcNAc-phosphotransferase \u03b1\/\u03b2\u2013subunits precursor gene. Am. J. Hum. Genet. 78, 451\u2013463 (2006).","journal-title":"Am. J. Hum. Genet."},{"key":"173_CR44","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1111\/j.1399-0004.2007.00954.x","volume":"73","author":"M Plante","year":"2008","unstructured":"Plante, M. et al. Mucolipidosis II: a single causal mutation in the N\u2010acetylglucosamine\u20101\u2010phosphotransferase gene (GNPTAB) in a French Canadian founder population. Clin. Genet. 73, 236\u2013244 (2008).","journal-title":"Clin. Genet."},{"key":"173_CR45","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1111\/j.1399-0004.2009.01185.x","volume":"76","author":"M Encarna\u00e7\u00e3o","year":"2009","unstructured":"Encarna\u00e7\u00e3o, M. et al. Molecular analysis of the GNPTAB and GNPTG genes in 13 patients with mucolipidosis type II or type III\u2013identification of eight novel mutations. Clin. Genet. 76, 76\u201384 (2009).","journal-title":"Clin. Genet."},{"key":"173_CR46","doi-asserted-by":"publisher","first-page":"3497","DOI":"10.1093\/hmg\/ddv100","volume":"24","author":"RV Velho","year":"2015","unstructured":"Velho, R. V. et al. Analyses of disease-related GNPTAB mutations define a novel GlcNAc-1-phosphotransferase interaction domain and an alternative site-1 protease cleavage site. Hum. Mol. Genet. 24, 3497\u20133505 (2015).","journal-title":"Hum. Mol. Genet."},{"key":"173_CR47","doi-asserted-by":"publisher","first-page":"1109","DOI":"10.1038\/nm1305","volume":"11","author":"S Tiede","year":"2005","unstructured":"Tiede, S. et al. Mucolipidosis II is caused by mutations in GNPTA encoding the \u03b1\/\u03b2 GlcNAc-1-phosphotransferase. Nat. Med. 11, 1109\u20131112 (2005).","journal-title":"Nat. Med."},{"key":"173_CR48","doi-asserted-by":"publisher","first-page":"2661","DOI":"10.1093\/brain\/aws209","volume":"135","author":"K Kollmann","year":"2012","unstructured":"Kollmann, K. et al. Lysosomal dysfunction causes neurodegeneration in mucolipidosis II \u2018knock-in\u2019mice. Brain 135, 2661\u20132675 (2012).","journal-title":"Brain"},{"key":"173_CR49","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1016\/j.ymgme.2006.03.003","volume":"88","author":"R Bargal","year":"2006","unstructured":"Bargal, R. et al. When Mucolipidosis III meets Mucolipidosis II: GNPTA gene mutations in 24 patients. Mol. Genet. Metab. 88, 359\u2013363 (2006).","journal-title":"Mol. Genet. Metab."},{"key":"173_CR50","doi-asserted-by":"publisher","first-page":"308","DOI":"10.1002\/humu.20205","volume":"26","author":"KH Paik","year":"2005","unstructured":"Paik, K. H. et al. Identification of mutations in the GNPTA (MGC4170) gene coding for GlcNAc\u2010phosphotransferase \u03b1\/\u03b2 subunits in Korean patients with mucolipidosis type II or type IIIA. Hum. Mutat. 26, 308\u2013314 (2005).","journal-title":"Hum. Mutat."},{"key":"173_CR51","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.ymgme.2007.09.010","volume":"93","author":"B Tappino","year":"2008","unstructured":"Tappino, B., Regis, S., Corsolini, F. & Filocamo, M. An Alu insertion in compound heterozygosity with a microduplication in GNPTAB gene underlies Mucolipidosis II. Mol. Genet. Metab. 93, 129\u2013133 (2008).","journal-title":"Mol. Genet. Metab."},{"key":"173_CR52","unstructured":"Forsythe, E. & Beales, P. L. in GeneReviews\u00ae[Internet] (University of Washington, Seattle, 2015)."},{"key":"173_CR53","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/ng935","volume":"31","author":"K Mykytyn","year":"2002","unstructured":"Mykytyn, K. et al. Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome. Nat. Genet. 31, 435\u2013438 (2002).","journal-title":"Nat. Genet."},{"key":"173_CR54","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1086\/346172","volume":"72","author":"K Mykytyn","year":"2003","unstructured":"Mykytyn, K. et al. Evaluation of complex inheritance involving the most common Bardet-Biedl syndrome locus (BBS1). Am. J. Hum. Genet. 72, 429\u2013437 (2003).","journal-title":"Am. J. Hum. Genet."},{"key":"173_CR55","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1086\/375178","volume":"72","author":"PL Beales","year":"2003","unstructured":"Beales, P. L. et al. Genetic interaction of BBS1 mutations with alleles at other BBS loci can result in non-Mendelian Bardet-Biedl syndrome. Am. J. Hum. Genet. 72, 1187\u20131199 (2003).","journal-title":"Am. J. Hum. Genet."},{"key":"173_CR56","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1002\/humu.21509","volume":"32","author":"F Schmid","year":"2011","unstructured":"Schmid, F. et al. U1 snRNA\u2010mediated gene therapeutic correction of splice defects caused by an exceptionally mild BBS mutation. Hum. Mutat. 32, 815\u2013824 (2011).","journal-title":"Hum. Mutat."},{"key":"173_CR57","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1212\/WNL.0b013e3182a4a518","volume":"81","author":"A Echaniz-Laguna","year":"2013","unstructured":"Echaniz-Laguna, A. et al. SURF1 deficiency causes demyelinating Charcot-Marie-Tooth disease. Neurology 81, 1523\u20131530 (2013).","journal-title":"Neurology"},{"key":"173_CR58","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/3804","volume":"20","author":"Z Zhu","year":"1998","unstructured":"Zhu, Z. et al. SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome. Nat. Genet. 20, 337\u2013343 (1998).","journal-title":"Nat. Genet."},{"key":"173_CR59","first-page":"194","volume":"106","author":"A Poyau","year":"2000","unstructured":"Poyau, A. et al. Missense mutations in SURF1 associated with deficient cytochrome c oxidase assembly in Leigh syndrome patients. Hum. Genet. 106, 194\u2013205 (2000).","journal-title":"Hum. Genet."},{"key":"173_CR60","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1002\/humu.1112","volume":"17","author":"MO P\u00e9quignot","year":"2001","unstructured":"P\u00e9quignot, M. O. et al. Mutations in the SURF1 gene associated with Leigh syndrome and cytochrome c oxidase deficiency. Hum. Mutat. 17, 374\u2013381 (2001).","journal-title":"Hum. Mutat."},{"key":"173_CR61","doi-asserted-by":"publisher","first-page":"1192","DOI":"10.1002\/humu.22095","volume":"33","author":"IC Lee","year":"2012","unstructured":"Lee, I. C. et al. SURF1\u2010associated leigh syndrome: a case series and novel mutations. Hum. Mutat. 33, 1192\u20131200 (2012).","journal-title":"Hum. Mutat."},{"key":"173_CR62","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1002\/ana.1060","volume":"49","author":"S Rahman","year":"2001","unstructured":"Rahman, S., Brown, R. M., Chong, W. K., Wilson, C. J. & Brown, G. K. A SURF1 gene mutation presenting as isolated leukodystrophy. Ann. Neurol.: Off. J. Am. Neurological Assoc. Child Neurol. Soc. 49, 797\u2013800 (2001).","journal-title":"Ann. Neurol.: Off. J. Am. Neurological Assoc. Child Neurol. Soc."},{"key":"173_CR63","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.ajhg.2009.06.004","volume":"85","author":"AJ Verkerk","year":"2009","unstructured":"Verkerk, A. J. et al. Mutation in the AP4M1 gene provides a model for neuroaxonal injury in cerebral palsy. Am. J. Hum. Genet. 85, 40\u201352 (2009).","journal-title":"Am. J. Hum. Genet."},{"key":"173_CR64","first-page":"1","volume":"21","author":"W-C Ruan","year":"2020","unstructured":"Ruan, W.-C. et al. Novel variants in AP4B1 cause spastic tetraplegia, moderate psychomotor development delay and febrile seizures in a Chinese patient: a case report. BMC Med. Genet. 21, 1\u20136 (2020).","journal-title":"BMC Med. Genet."},{"key":"173_CR65","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41746-019-0191-0","volume":"2","author":"M Uddin","year":"2019","unstructured":"Uddin, M., Wang, Y. & Woodbury-Smith, M. Artificial intelligence for precision medicine in neurodevelopmental disorders. npj Digital Med. 2, 1\u201310 (2019).","journal-title":"npj Digital Med."},{"key":"173_CR66","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","volume":"25","author":"H Li","year":"2009","unstructured":"Li, H. & Durbin, R. Fast and accurate short read alignment with Burrows\u2013Wheeler transform. Bioinformatics 25, 1754\u20131760 (2009).","journal-title":"Bioinformatics"},{"key":"173_CR67","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. 20, 1297\u20131303 (2010).","journal-title":"Genome Res."},{"key":"173_CR68","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/0022-2836(75)90213-2","volume":"94","author":"F Sanger","year":"1975","unstructured":"Sanger, F. & Coulson, A. R. A rapid method for determining sequences in DNA by primed synthesis with DNA polymerase. J. Mol. Biol. 94, 441\u2013448 (1975).","journal-title":"J. Mol. Biol."}],"container-title":["npj Genomic Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41525-021-00173-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41525-021-00173-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41525-021-00173-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T20:47:52Z","timestamp":1670014072000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41525-021-00173-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,16]]},"references-count":68,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["173"],"URL":"https:\/\/doi.org\/10.1038\/s41525-021-00173-0","relation":{},"ISSN":["2056-7944"],"issn-type":[{"value":"2056-7944","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,16]]},"assertion":[{"value":"31 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 February 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"M.U. is on the Scientific Advisory Committees of GenomeArc Inc., and NeuroGen Children\u2019s Healthcare. S.W.S. is on the Scientific Advisory Committees of Deep Genomics, Population Bio and is a Highly Cited Academic Advisor to the King Abdulaziz University. The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14"}}