{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:12:33Z","timestamp":1793059953206,"version":"4.5.0"},"reference-count":30,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T00:00:00Z","timestamp":1676419200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Spondyloocular syndrome (SOS, OMIM # 605822) is a rare genetic disorder characterized by osseous and ocular manifestations, including generalized osteoporosis, multiple long bones fractures, platyspondyly, dense cataracts and retinal detachment, and dysmorphic facial features, with or without short stature, cardiopathy, hearing impairment, and intellectual disability. Biallelic mutations in the XYLT2 gene (OMIM * 608125), encoding the xylosyltransferase II, were shown to be responsible for this disease. To date, 22 cases with SOS have been described, with varying clinical presentations and a yet-to-be-established genotypic\u2013phenotypic correlation. Two patients from a consanguineous Lebanese family that presented with SOS were included in this study. Whole exome sequencing revealed a novel homozygous nonsense mutation in XYLT2 (p.Tyr414*) in these patients. We review all previously reported cases with SOS, describe the second nonsense mutation in XYLT2, and contribute to a better delineation of the phenotypic spectrum of the disease.<\/jats:p>","DOI":"10.3390\/genes14020497","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T02:28:27Z","timestamp":1676514507000},"page":"497","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Spondyloocular Syndrome: A Report of an Additional Family and Phenotypic Spectrum Delineation"],"prefix":"10.3390","volume":"14","author":[{"given":"Eliane","family":"Chouery","sequence":"first","affiliation":[{"name":"Department of Human Genetics, Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos P.O. Box 13-5053, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rim","family":"Karam","sequence":"additional","affiliation":[{"name":"Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos P.O. Box 13-5053, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9026-0807","authenticated-orcid":false,"given":"Yves Najm","family":"Mrad","sequence":"additional","affiliation":[{"name":"Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos P.O. Box 13-5053, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cybel","family":"Mehawej","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos P.O. Box 13-5053, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nahia","family":"Dib El Jalbout","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Lebanese American University Medical Center, Rizk Hospital, Beirut P.O. Box 13-5053, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamal","family":"Bleik","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Lebanese American University Medical Center, Rizk Hospital, Beirut P.O. Box 13-5053, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Mahfoud","sequence":"additional","affiliation":[{"name":"Department of Radiology, Gilbert and Rose-Marie Ghagoury School of Medicine, Lebanese American University, Byblos P.O. Box 13-5053, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0714-2469","authenticated-orcid":false,"given":"Andre","family":"Megarbane","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Gilbert and Rose-Marie Chagoury School of Medicine, Lebanese American University, Byblos P.O. Box 13-5053, Lebanon"},{"name":"Institut J\u00e9r\u00f4me Lejeune, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1034\/j.1399-0004.2001.590206.x","article-title":"Retinal detachment and cataract, facial dysmorphism, generalized osteoporosis, immobile spine and platyspondyly in a consanguinous kindred\u2014A possible new syndrome: A possible new spondylo-ocular syndrome","volume":"59","author":"Schmidt","year":"2001","journal-title":"Clin. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.ajhg.2015.04.017","article-title":"Homozygosity for Frameshift Mutations in XYLT2 Result in a Spondylo-Ocular Syndrome with Bone Fragility, Cataracts, and Hearing Defects","volume":"96","author":"Munns","year":"2015","journal-title":"Am. J. Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"824445","DOI":"10.3389\/fgene.2022.824445","article-title":"Mutant B3GALT6 in a Multiplex Family: A Dominant Variant Co-Segregated With Moderate Malformations","volume":"13","author":"Shen","year":"2022","journal-title":"Front. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1055\/s-0042-118706","article-title":"Abnormal Proteoglycan Synthesis Due to Gene Defects Causes Skeletal Diseases with Overlapping Phenotypes","volume":"48","author":"Taylan","year":"2016","journal-title":"Horm. Metab. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s10545-017-0050-6","article-title":"What is new in CDG?","volume":"40","author":"Jaeken","year":"2017","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.1002\/ajmg.a.37209","article-title":"A homozygous B3GAT3 mutation causes a severe syndrome with multiple fractures, expanding the phenotype of linkeropathy syndromes","volume":"167","author":"Jones","year":"2015","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1093\/nar\/16.3.1215","article-title":"A simple salting out procedure for extracting DNA from human nucleated cells","volume":"16","author":"Miller","year":"1988","journal-title":"Nucleic Acids Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1093\/bioinformatics\/btp324","article-title":"Fast and accurate short read alignment with Burrows-Wheeler transform","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"W545","DOI":"10.1093\/nar\/gky471","article-title":"VarAFT: A variant annotation and filtration system for human next generation sequencing data","volume":"46","author":"Desvignes","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_11","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"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","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."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1111\/cge.13179","article-title":"Homozygous XYLT2 variants as a cause of spondyloocular syndrome","volume":"93","author":"Umair","year":"2018","journal-title":"Clin. Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"103585","DOI":"10.1016\/j.ejmg.2018.11.019","article-title":"Intrafamilial variability of XYLT2-related spondyloocular syndrome","volume":"62","author":"Guleray","year":"2019","journal-title":"Eur. J. Med. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1002\/jbmr.2834","article-title":"Spondyloocular Syndrome: Novel Mutations in XYLT2 Gene and Expansion of the Phenotypic Spectrum: XYLT2 GENE MUTATIONS IN SPONDYLOOCULAR SYNDROME","volume":"31","author":"Taylan","year":"2016","journal-title":"J. Bone Miner. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3195","DOI":"10.1002\/ajmg.a.38470","article-title":"Two novel mutations in XYLT2 cause spondyloocular syndrome","volume":"173","author":"Taylan","year":"2017","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"144","DOI":"10.3389\/fgene.2019.00144","article-title":"A Novel Homozygous Frameshift Variant in XYLT2 Causes Spondyloocular Syndrome in a Consanguineous Pakistani Family","volume":"10","author":"Kausar","year":"2019","journal-title":"Front. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"761264","DOI":"10.3389\/fgene.2021.761264","article-title":"Spondyloocular Syndrome: A Novel XYLT2 Variant with Description of the Neonatal Phenotype","volume":"12","author":"Doddato","year":"2021","journal-title":"Front. Genet."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1186\/s13023-021-02032-8","article-title":"Long-term effectiveness of carglumic acid in patients with propionic acidemia (PA) and methylmalonic acidemia (MMA): A randomized clinical trial","volume":"16","author":"Alfadhel","year":"2021","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1159\/000365889","article-title":"The Use of Bisphosphonates in Pediatrics","volume":"82","author":"Baroncelli","year":"2014","journal-title":"Horm. Res. Paediatr."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Ritelli, M., Cinquina, V., Giacopuzzi, E., Venturini, M., Chiarelli, N., and Colombi, M. (2019). Further Defining the Phenotypic Spectrum of B3GAT3 Mutations and Literature Review on Linkeropathy Syndromes. Genes, 10.","DOI":"10.3390\/genes10090631"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Li, Y., Zhang, C., Zhang, H., Feng, W., Wang, Q., and Fan, R. (2022). Severe phenotypes of B3GAT3-related disorder caused by two heterozygous variants: A case report and literature review. BMC Med. Genomics, 15.","DOI":"10.1186\/s12920-022-01160-9"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1002\/ajmg.a.35445","article-title":"A newly recognized syndrome with characteristic facial features, skeletal dysplasia, and developmental delay","volume":"158A","author":"Baratela","year":"2012","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1038\/jhg.2016.143","article-title":"Novel and recurrent XYLT1 mutations in two Turkish families with Desbuquois dysplasia, type 2","volume":"62","author":"Guo","year":"2017","journal-title":"J. Hum. Genet."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"104342","DOI":"10.1016\/j.ejmg.2021.104342","article-title":"B3GAT3-related linkeropathy and an in-frame homozygous deletion in an adult patient","volume":"64","author":"Bolund","year":"2021","journal-title":"Eur. J. Med. Genet."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1111\/cge.13236","article-title":"A B3GALT6 variant in patient originally described as Al-Gazali syndrome and implicating the endoplasmic reticulum quality control in the mechanism of some \u03b23GalT6-pathy mutations","volume":"93","author":"John","year":"2018","journal-title":"Clin. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"28841","DOI":"10.1074\/jbc.274.41.28841","article-title":"Molecular basis for the progeroid variant of Ehlers-Danlos syndrome. Identification and characterization of two mutations in galactosyltransferase I gene","volume":"274","author":"Okajima","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/(SICI)1096-8628(19990917)86:3<245::AID-AJMG10>3.0.CO;2-5","article-title":"Spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL): Presentation in two unrelated patients in the United States","volume":"86","author":"Smith","year":"1999","journal-title":"Am. J. Med. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Bizzari, S., Nair, P., Deepthi, A., Hana, S., Al-Ali, M.T., Megarban\u00e9, A., and El-Hayek, S. (2021). Catalogue for Transmission Genetics in Arabs (CTGA) Database: Analysing Lebanese Data on Genetic Disorders. Genes, 12.","DOI":"10.3390\/genes12101518"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1047474","DOI":"10.3389\/fgene.2022.1047474","article-title":"Non-invasive prenatal testing for autosomal recessive disorders: A new promising approach","volume":"13","author":"Alyafee","year":"2022","journal-title":"Front. Genet."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/2\/497\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:37:02Z","timestamp":1760121422000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/2\/497"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,15]]},"references-count":30,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2023,2]]}},"alternative-id":["genes14020497"],"URL":"https:\/\/doi.org\/10.3390\/genes14020497","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,15]]}}}