The missing "link": an autosomal recessive short stature syndrome caused by a hypofunctional XYLT1 mutation

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dc.contributor.authorSchreml, Julia
dc.contributor.authorDurmaz, Burak
dc.contributor.authorCogulu, Ozgur
dc.contributor.authorKeupp, Katharina
dc.contributor.authorBeleggia, Filippo
dc.contributor.authorPohl, Esther
dc.contributor.authorMilz, Esther
dc.contributor.authorCoker, Mahmut
dc.contributor.authorUcar, Sema Kalkan
dc.contributor.authorNuernberg, Gudrun
dc.contributor.authorNuernberg, Peter
dc.contributor.authorKuhn, Joachim
dc.contributor.authorÖzkınay, Ferda
dc.date.accessioned2019-10-27T22:06:23Z
dc.date.available2019-10-27T22:06:23Z
dc.date.issued2014
dc.departmentEge Üniversitesien_US
dc.description.abstractProteoglycan (PG) synthesis begins with the sequential addition of a "linker chain", made up of four sugar residues, to a specific region of a core protein. Defects in the enzymes catalyzing steps two to four of the linker chain synthesis have been shown to cause autosomal recessive human phenotypes while no mutation has yet been reported in humans for the xylosyltransferases 1 and 2 (XT1 and XT2), the initiating enzymes in the linker chain formation. Here, we present a consanguineous Turkish family with two affected individuals presenting with short stature, distinct facial features, alterations of fat distribution, and moderate intellectual disability. X-rays showed only mild skeletal changes in the form of a short femoral neck, stocky and plump long bones and thickened ribs. Using a combination of whole-exome sequencing (WES), determination of homozygous stretches by WES variants, and classical linkage analysis, we identified the homozygous missense mutation c.C1441T in XYLT1, encoding XT1, within a large homozygous stretch on chromosome 16p13.12-p12.1. The mutation co-segregated with the phenotype in the family, is not found in over 13,000 alleles in the exome variant server and is predicted to change a highly conserved arginine at position 481 (p.R481W) located in the putative catalytical domain. Immunostaining of primary patient fibroblasts showed a loss of predominance of Golgi localization in mutant cells. Moreover, western blot analysis of decorin in cell culture supernatant demonstrated glycosylation differences between patient and control cells. Our data provide evidence that functional alterations of XT1 cause an autosomal recessive short stature syndrome associated with intellectual disability.en_US
dc.identifier.doi10.1007/s00439-013-1351-yen_US
dc.identifier.endpage39en_US
dc.identifier.issn0340-6717
dc.identifier.issn1432-1203
dc.identifier.issue1en_US
dc.identifier.pmid23982343en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage29en_US
dc.identifier.urihttps://doi.org/10.1007/s00439-013-1351-y
dc.identifier.urihttps://hdl.handle.net/11454/48790
dc.identifier.volume133en_US
dc.identifier.wosWOS:000329244500003en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpringeren_US
dc.relation.ispartofHuman Geneticsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.titleThe missing "link": an autosomal recessive short stature syndrome caused by a hypofunctional XYLT1 mutationen_US
dc.typeArticleen_US

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