title: Spondyloocular Syndrome: Novel Mutations in XYLT2 Gene and Expansion of the Phenotypic Spectrum.
abstract: Spondyloocular syndrome is an autosomal-recessive disorder with spinal compression fractures, osteoporosis, and cataract. Mutations in XYLT2, encoding isoform of xylosyltransferase, were recently identified as the cause of the syndrome. We report on 4 patients, 2 unrelated patients and 2 siblings, with spondyloocular syndrome and novel mutations in XYLT2. Exome sequencing revealed a homozygous nonsense mutation, NM_022167.3(XYLT2): c.2188C>T, resulting in a premature stop codon (p.Arg730*) in a female patient. The patient presents visual impairment, generalized osteoporosis, short stature with short trunk, spinal compression fractures, and increased intervertebral disc space and hearing loss. We extended our XYLT2 analysis to a cohort of 22 patients with generalized osteoporosis, mostly from consanguineous families. In this cohort, we found by Sanger sequencing 2 siblings and 1 single patient who were homozygous for missense mutations in the XYLT2 gene (p.Arg563Gly and p.Leu605Pro). The patients had osteoporosis, compression fractures, cataracts, and hearing loss. Bisphosphonate treatment in 1 patient resulted in almost complete normalization of vertebral structures by adolescence, whereas treatment response in the others was variable. This report together with a previous study shows that mutations in the XYLT2 gene result in a variable phenotype dominated by spinal osteoporosis, cataract, and hearing loss. © 2016 American Society for Bone and Mineral Research.
authors.affiliation: Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Fulya
authors.initials: F
authors.lastname: Taylan
authors.affiliation: Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Alice
authors.initials: A
authors.lastname: Costantini
authors.affiliation: Department of Pediatric Endocrinology of Metabolism, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: Coles
authors.affiliation: Folkhälsan Institute of Genetics, Helsinki, Finland.
authors.forename: Minna
authors.initials: M
authors.lastname: Pekkinen
authors.affiliation: Department of Pediatric Endocrinology of Metabolism, The Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Elise
authors.initials: E
authors.lastname: Héon
authors.affiliation: Department of Pediatric Endocrinology, School of Medicine, Ankara University, Ankara, Turkey.
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Şıklar
authors.affiliation: Department of Pediatric Endocrinology, School of Medicine, Ankara University, Ankara, Turkey.
authors.forename: Merih
authors.initials: M
authors.lastname: Berberoğlu
authors.affiliation: Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Kämpe
authors.affiliation: Department of Pediatric Metabolism, Cerrahpasa Medicine School, Istanbul University, Istanbul, Turkey.
authors.forename: Ertuğrul
authors.initials: E
authors.lastname: Kıykım
authors.affiliation: Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.|Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Giedre
authors.initials: G
authors.lastname: Grigelioniene
authors.affiliation: Department of Pediatric Genetics, Cerrahpasa Medicine School, Istanbul University, Istanbul, Turkey.
authors.forename: Beyhan
authors.initials: B
authors.lastname: Tüysüz
authors.affiliation: Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.|Folkhälsan Institute of Genetics, Helsinki, Finland.|Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden.|Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: Outi
authors.initials: O
authors.lastname: Mäkitie
mesh_terms: D000293:Adolescent; D002386:Cataract / Q000150:complications / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D010024:Osteoporosis / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D010430:Pentosyltransferases / Q000235:genetics*; D010641:Phenotype; D016103:Spinal Fractures / Q000150:complications / Q000000981:diagnostic imaging / Q000235:genetics*; D013577:Syndrome; D000073359:Exome Sequencing; D000097608:UDP Xylose-Protein Xylosyltransferase
chemical_list: D010430:Pentosyltransferases; D000097608:UDP Xylose-Protein Xylosyltransferase
keywords: CATARACT; HEARING LOSS; OSTEOPOROSIS; PLATYSPONDYLY; WHOLE-EXOME SEQUENCING