{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:51:28Z","timestamp":1760241088182,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T00:00:00Z","timestamp":1574899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009045","name":"Uniwersytet Jagiello\u0144ski Collegium Medicum","doi-asserted-by":"publisher","award":["K\/ZDS\/004416"],"award-info":[{"award-number":["K\/ZDS\/004416"]}],"id":[{"id":"10.13039\/100009045","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Anterior segment dysgenesis (ASD) encompasses a spectrum of ocular disorders affecting the structures of the anterior eye chamber. Mutations in several genes, involved in eye development, are implicated in this disorder. ASD is often accompanied by diverse multisystemic symptoms and another genetic cause, such as variants in genes encoding collagen type IV. Thus, a wide spectrum of phenotypes and underlying genetic diversity make fast and proper diagnosis challenging. Here, we used AMELIE, an automatic text mining tool that enriches data with the most up-to-date information from literature, and wANNOVAR, which is based on well-documented databases and incorporates variant filtering strategy to identify genetic variants responsible for severely-manifested ASD in a newborn child. This strategy, applied to trio sequencing data in compliance with ACMG 2015 guidelines, helped us find two compound heterozygous variants of the B3GLCT gene, of which c.660+1G&gt;A (rs80338851) was previously associated with the phenotype of Peters plus syndrome (PPS), while the second, NM_194318.3:c.755delC (p.T252fs), in exon 9 of the same gene was noted for the first time. PPS, a very rare subtype of ASD, is a glycosylation disorder, where the dysfunctional B3GLCT gene product, O-fucose-specific \u03b2-1,3-glucosyltransferase, is ineffective in providing a noncanonical quality control system for proper protein folding in cells. Our study expands the mutation spectrum of the B3GLCT gene related to PPS. We suggest that the implementation of automatic text mining tools in combination with careful variant filtering could help translate sequencing results into diagnosis, thus, considerably accelerating the diagnostic process and, thereby, improving patient management.<\/jats:p>","DOI":"10.3390\/ijms20236006","type":"journal-article","created":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T10:54:10Z","timestamp":1574938450000},"page":"6006","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Contribution of a Novel B3GLCT Variant to Peters Plus Syndrome Discovered by a Combination of Next-Generation Sequencing and Automated Text Mining"],"prefix":"10.3390","volume":"20","author":[{"given":"Justyna","family":"Toto\u0144-\u017bura\u0144ska","sequence":"first","affiliation":[{"name":"Center for Medical Genomics\u2013OMICRON, Jagiellonian University Medical College, ul. Kopernika 7c, 31\u2013034 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4467-1175","authenticated-orcid":false,"given":"Przemys\u0142aw","family":"Kapusta","sequence":"additional","affiliation":[{"name":"Center for Medical Genomics\u2013OMICRON, Jagiellonian University Medical College, ul. Kopernika 7c, 31\u2013034 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6993-8078","authenticated-orcid":false,"given":"Magda","family":"Rybak-Krzyszkowska","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Perinatology, The University Hospital in Krakow, ul. Kopernika 23, 31-501 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katarzyna","family":"Lorenc","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Jagiellonian University Medical College, ul. Kopernika 23, 31-501 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julita","family":"Machlowska","sequence":"additional","affiliation":[{"name":"Center for Medical Genomics\u2013OMICRON, Jagiellonian University Medical College, ul. Kopernika 7c, 31\u2013034 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Skalniak","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Jagiellonian University Medical College, ul. Kopernika 17, 31\u2013501 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4227-1349","authenticated-orcid":false,"given":"Erita","family":"Filipek","sequence":"additional","affiliation":[{"name":"Clinic and Department of Pediatric Ophthalmology, School of Medicine in Katowice, Medical University of Silesia in Katowice, ul. Ceglana 35, 40-514 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorota","family":"Pawlik","sequence":"additional","affiliation":[{"name":"Department of Neonatology, Jagiellonian University Medical College, ul. Kopernika 23, 31-501 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9322-5545","authenticated-orcid":false,"given":"Pawe\u0142 P.","family":"Wo\u0142kow","sequence":"additional","affiliation":[{"name":"Center for Medical Genomics\u2013OMICRON, Jagiellonian University Medical College, ul. Kopernika 7c, 31\u2013034 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,28]]},"reference":[{"key":"ref_1","first-page":"405","article-title":"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","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med. Off. J. Am. Coll. Med. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/ceo.12152","article-title":"Genomics and anterior segment dysgenesis: A review","volume":"42","author":"Ito","year":"2014","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/S0002-9394(02)01401-0","article-title":"Endothelial dystrophy, iris hypoplasia, congenital cataract, and stromal thinning (edict) syndrome maps to chromosome 15q22.1\u2013q25.3","volume":"134","author":"Jun","year":"2002","journal-title":"Am. J. Ophthalmol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/ejhg.2014.119","article-title":"Novel mutations in PXDN cause microphthalmia and anterior segment dysgenesis","volume":"23","author":"Choi","year":"2015","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1002\/humu.23395","article-title":"Mutation update of transcription factor genes FOXE3, HSF4, MAF, and PITX3 causing cataracts and other developmental ocular defects","volume":"39","author":"Anand","year":"2018","journal-title":"Hum. Mutat."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1387\/ijdb.041865dg","article-title":"Anterior segment development relevant to glaucoma","volume":"48","author":"Gould","year":"2004","journal-title":"Int. J. Dev. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Micheal, S., Siddiqui, S.N., Zafar, S.N., Villanueva-Mendoza, C., Cort\u00e9s-Gonz\u00e1lez, V., Khan, M.I., and den Hollander, A.I. (2016). A Novel Homozygous Mutation in FOXC1 Causes Axenfeld Rieger Syndrome with Congenital Glaucoma. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0160016"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1007\/s00439-014-1481-x","article-title":"Whole exome sequence analysis of Peters anomaly","volume":"133","author":"Weh","year":"2014","journal-title":"Hum. Genet."},{"key":"ref_9","first-page":"843","article-title":"The expanding phenotype of COL4A1 and COL4A2 mutations: Clinical data on 13 newly identified families and a review of the literature","volume":"17","author":"Meuwissen","year":"2015","journal-title":"Genet. Med. Off. J. Am. Coll. Med. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1534\/genetics.106.064733","article-title":"Type IV Procollagen Missense Mutations Associated with Defects of the Eye, Vascular Stability, the Brain, Kidney Function and Embryonic or Postnatal Viability in the Mouse, Mus musculus: An Extension of the Col4a1 Allelic Series and the Identification of the First Two Col4a2 Mutant Alleles","volume":"175","author":"Favor","year":"2007","journal-title":"Genetics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1097\/ICU.0b013e328349412b","article-title":"Genetics of anterior segment dysgenesis disorders","volume":"22","author":"Reis","year":"2011","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Birgmeier, J., Haeussler, M., Deisseroth, C.A., Jagadeesh, K.A., Ratner, A.J., Guturu, H., Wenger, A.M., Stenson, P.D., Cooper, D.N., and Re, C. (2017). AMELIE accelerates Mendelian patient diagnosis directly from the primary literature. bioRxiv, 171322.","DOI":"10.1101\/171322"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: Functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1136\/jmedgenet-2012-100918","article-title":"wANNOVAR: Annotating genetic variants for personal genomes via the web","volume":"49","author":"Chang","year":"2012","journal-title":"J. Med. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1556","DOI":"10.1038\/nprot.2015.105","article-title":"Genomic variant annotation and prioritization with ANNOVAR and wANNOVAR","volume":"10","author":"Yang","year":"2015","journal-title":"Nat. Protoc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1038\/d41586-018-06958-1","article-title":"The clinical code-breakers","volume":"562","author":"Eisenstein","year":"2018","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1056\/NEJMoa1306555","article-title":"Clinical Whole-Exome Sequencing for the Diagnosis of Mendelian Disorders","volume":"369","author":"Yang","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1880","DOI":"10.1001\/jama.2014.14604","article-title":"Clinical Exome Sequencing for Genetic Identification of Rare Mendelian Disorders","volume":"312","author":"Lee","year":"2014","journal-title":"JAMA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/gim.2014.154","article-title":"Enhanced utility of family-centered diagnostic exome sequencing with inheritance model\u2013based analysis: Results from 500 unselected families with undiagnosed genetic conditions","volume":"17","author":"Farwell","year":"2015","journal-title":"Genet. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2004","DOI":"10.1038\/nprot.2015.124","article-title":"Next-generation diagnostics and disease-gene discovery with the Exomiser","volume":"10","author":"Smedley","year":"2015","journal-title":"Nat. Protoc."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1038\/ejhg.2016.32","article-title":"Clinical utility gene card for: Peters plus syndrome","volume":"24","author":"Jaeken","year":"2016","journal-title":"Eur. J. Hum. Genet. EJHG"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Gilfix, B.M. (2019). Congenital disorders of glycosylation and the challenge of rare diseases. Hum. Mutat.","DOI":"10.1002\/humu.23829"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1001\/jamaophthalmol.2017.0046","article-title":"Association of Steroid 5\u03b1-Reductase Type 3 Congenital Disorder of Glycosylation with Early-Onset Retinal Dystrophy","volume":"135","author":"Taylor","year":"2017","journal-title":"JAMA Ophthalmol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1080\/07853890802301975","article-title":"Peters\u2019-plus syndrome is a congenital disorder of glycosylation caused by a defect in the \u03b21,3-glucosyltransferase that modifies thrombospondin type 1 repeats","volume":"41","author":"Heinonen","year":"2009","journal-title":"Ann. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1093\/glycob\/cwl035","article-title":"Molecular cloning and characterization of a novel human \u03b21,3-glucosyltransferase, which is localized at the endoplasmic reticulum and glucosylates O-linked fucosylglycan on thrombospondin type 1 repeat domain","volume":"16","author":"Sato","year":"2006","journal-title":"Glycobiology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.cub.2014.11.049","article-title":"Peters plus syndrome mutations disrupt a noncanonical ER quality-control mechanism","volume":"25","author":"Vasudevan","year":"2015","journal-title":"Curr. Biol. CB"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/ng.2578","article-title":"Seven new loci associated with age-related macular degeneration","volume":"45","author":"Fritsche","year":"2013","journal-title":"Nat. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1086\/507567","article-title":"Peters Plus syndrome is caused by mutations in B3GALTL, a putative glycosyltransferase","volume":"79","author":"Kriek","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/S0968-0004(98)01208-0","article-title":"A rule for termination-codon position within intron-containing genes: When nonsense affects RNA abundance","volume":"23","author":"Nagy","year":"1998","journal-title":"Trends Biochem. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/ng.3664","article-title":"The rules and impact of nonsense-mediated mRNA decay in human cancers","volume":"48","author":"Lindeboom","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1038\/sj.ejhg.5201649","article-title":"Nonsense-mediated mRNA decay modulates clinical outcome of genetic disease","volume":"14","author":"Khajavi","year":"2006","journal-title":"Eur. J. Hum. Genet. EJHG"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1093\/bioinformatics\/btp698","article-title":"Fast and accurate long-read alignment with Burrows-Wheeler transform","volume":"26","author":"Li","year":"2010","journal-title":"Bioinforma. Oxf. Engl."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"1000 Genome Project Data Processing Subgroup the Sequence Alignment\/Map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinforma. Oxf. Engl."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/ng.806","article-title":"A framework for variation discovery and genotyping using next-generation DNA sequencing data","volume":"43","author":"DePristo","year":"2011","journal-title":"Nat. Genet."},{"key":"ref_35","first-page":"11.10.1","article-title":"From FastQ data to high confidence variant calls: The Genome Analysis Toolkit best practices pipeline","volume":"43","author":"Carneiro","year":"2013","journal-title":"Curr. Protoc. Bioinform."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Paila, U., Chapman, B.A., Kirchner, R., and Quinlan, A.R. (2013). GEMINI: Integrative Exploration of Genetic Variation and Genome Annotations. PLOS Comput. Biol., 9.","DOI":"10.1371\/journal.pcbi.1003153"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3","volume":"6","author":"Cingolani","year":"2012","journal-title":"Fly (Austin)"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/nprot.2015.123","article-title":"SIFT missense predictions for genomes","volume":"11","author":"Vaser","year":"2016","journal-title":"Nat. Protoc."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Choi, Y., Sims, G.E., Murphy, S., Miller, J.R., and Chan, A.P. (2012). Predicting the functional effect of amino acid substitutions and indels. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0046688"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1093\/bioinformatics\/btx536","article-title":"FATHMM-XF: Accurate prediction of pathogenic point mutations via extended features","volume":"34","author":"Rogers","year":"2018","journal-title":"Bioinformatics"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nmeth.2890","article-title":"MutationTaster2: Mutation prediction for the deep-sequencing age","volume":"11","author":"Schwarz","year":"2014","journal-title":"Nat. Methods"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1038\/nmeth.3484","article-title":"Phenolyzer: Phenotype-based prioritization of candidate genes for human diseases","volume":"12","author":"Yang","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1093\/bioinformatics\/bty897","article-title":"VarSome: The human genomic variant search engine","volume":"35","author":"Kopanos","year":"2019","journal-title":"Bioinformatics"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/23\/6006\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:38:27Z","timestamp":1760189907000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/23\/6006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,28]]},"references-count":43,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["ijms20236006"],"URL":"https:\/\/doi.org\/10.3390\/ijms20236006","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2019,11,28]]}}}