ArticleAmerican journal of human genetics2015
Homozygosity for frameshift mutations in XYLT2 result in a spondylo-ocular syndrome with bone fragility, cataracts, and hearing defects.
Article in American journal of human genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 2 of them syntheses that pooled it.
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Who cites it
46 citing papers in PubMed, 2 syntheses or guidelines pooled it, 77 citations in OpenAlex.
- Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Cardiac complications of congenital disorders of glycosylation (CDG): a systematic review of the literature.Journal of inherited metabolic disease · 2017Pooled it
- Xylosyltransferase-I serum activity is a promising biomarker for postmenopausal osteoporosis.Scientific reports · 2026Article
- Spondylo-ocular syndrome: xylosyltransferase 2 gene mutation and clinical observations-a case report.Journal of medical case reports · 2026Article
- Xylosyltransferase engineering to manipulate proteoglycans in mammalian cells.Nature chemical biology · 2026Article
- Sex-specific association between osteoporosis and cataracts: UK Biobank and Hong Kong Osteoporosis Study.Archives of osteoporosis · 2026Article
- Xylosyltransferase-II deficiency rewires innate immune signaling and destabilizes polarization in human macrophages.Frontiers in immunology · 2026Article
- Congenital disorders caused by aberrations in the biosynthesis of chondroitin/dermatan sulfate.Journal of human genetics · 2025Review
- mRNA Degradation as a Therapeutic Solution for Mucopolysaccharidosis Type IIIC: Use of Antisense Oligonucleotides to Promote Downregulation of Heparan Sulfate Synthesis.International journal of molecular sciences · 2025Article
- A Dyadic Nosology for Osteogenesis Imperfecta and Bone Fragility Syndromes 2024.Calcified tissue international · 2024Review
- Cardiac Molecular Analysis Reveals Aging-Associated Metabolic Alterations Promoting Glycosaminoglycans Accumulation via Hexosamine Biosynthetic Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Spondyloocular Syndrome: First Case of Rare Osseous and Ocular Syndrome from India with Novel Mutation and Expanded Phenotypic Spectrum.Calcified tissue international · 2024Article
- Xylosyltransferase-Deficiency in Human Dermal Fibroblasts Induces Compensatory Myofibroblast Differentiation and Long-Term ECM Reduction.Biomedicines · 2024Article
- Cardiac Molecular Analysis Reveals Aging-Associated Metabolic Alterations Promoting Glycosaminoglycans Accumulation Via Hexosamine Biosynthetic Pathway.bioRxiv : the preprint server for biology · 2023Article
- Japanese medaka Olpax6.1 mutant as a potential model for spondylo-ocular syndrome.Functional & integrative genomics · 2023Article
- Spondyloocular Syndrome: A Report of an Additional Family and Phenotypic Spectrum Delineation.Genes · 2023Review
- Pathogenic Roles of Heparan Sulfate and Its Use as a Biomarker in Mucopolysaccharidoses.International journal of molecular sciences · 2022Review
- Spondylo-ocular Syndrome Due to a Novel Variant inJournal of pediatric genetics · 2022Article
- Novel compound heterozygous variants in XYLT1 gene caused Desbuquois dysplasia type 2 in an aborted fetus: a case report.BMC pediatrics · 2022Article
- MutantFrontiers in genetics · 2022Article
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
Heparan and chondroitin/dermatan sulfated proteoglycans have a wide range of roles in cellular and tissue homeostasis including growth factor function, morphogen gradient formation, and co-receptor activity. Proteoglycan assembly initiates with a xylose monosaccharide covalently attached by either xylosyltransferase I or II. Three individuals from two families were found that exhibited similar phenotypes. The index case subjects were two brothers, individuals 1 and 2, who presented with osteoporosis, cataracts, sensorineural hearing loss, and mild learning defects. Whole exome sequence analyses showed that both individuals had a homozygous c.692dup mutation (GenBank: NM_022167.3) in the xylosyltransferase II locus (XYLT2) (MIM: 608125), causing reduced XYLT2 mRNA and low circulating xylosyltransferase (XylT) activity. In an unrelated boy (individual 3) from the second family, we noted low serum XylT activity. Sanger sequencing of XYLT2 in this individual revealed a c.520del mutation in exon 2 that resulted in a frameshift and premature stop codon (p.Ala174Profs(∗)35). Fibroblasts from individuals 1 and 2 showed a range of defects including reduced XylT activity, GAG incorporation of (35)SO4, and heparan sulfate proteoglycan assembly. These studies demonstrate that human XylT2 deficiency results in vertebral compression fractures, sensorineural hearing loss, eye defects, and heart defects, a phenotype that is similar to the autosomal-recessive disorder spondylo-ocular syndrome of unknown cause. This phenotype is different from what has been reported in individuals with other linker enzyme deficiencies. These studies illustrate that the cells of the lens, retina, heart muscle, inner ear, and bone are dependent on XylT2 for proteoglycan assembly in humans.
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Registered trials
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