Mutations in B3GALT6, which Encodes a Glycosaminoglycan Linker Region Enzyme, Cause a Spectrum of Skeletal and Connective Tissue Disorders

dc.creatorNakajima, M
dc.creatorMizumoto, S
dc.creatorMiyake, N
dc.creatorKogawa, R
dc.creatorIida, A
dc.creatorIto, H
dc.creatorKitoh, H
dc.creatorHirayama, A
dc.creatorMitsubuchi, H
dc.creatorMiyazaki, O
dc.creatorKosaki, R
dc.creatorHorikawa, R
dc.creatorLai, A
dc.creatorMendoza-Londono, R
dc.creatorDupuis, L
dc.creatorChitayat, D
dc.creatorHoward, A
dc.creatorLeal, GE
dc.creatorCavalcanti, D
dc.creatorTsurusaki, Y
dc.creatorSaitsu, H
dc.creatorWatanabe, S
dc.creatorLausch, E
dc.creatorUnger, S
dc.creatorBonafe, L
dc.creatorOhashi, H
dc.creatorSuperti-Furga, A
dc.creatorMatsumoto, N
dc.creatorSugahara, K
dc.creatorNishimura, G
dc.creatorIkegawa, S
dc.date2013
dc.date38869
dc.date2014-08-01T18:39:33Z
dc.date2015-11-26T18:03:41Z
dc.date2014-08-01T18:39:33Z
dc.date2015-11-26T18:03:41Z
dc.date.accessioned2018-03-29T00:45:39Z
dc.date.available2018-03-29T00:45:39Z
dc.identifierAmerican Journal Of Human Genetics. Cell Press, v. 92, n. 6, n. 927, n. 934, 2013.
dc.identifier0002-9297
dc.identifierWOS:000320415300009
dc.identifier10.1016/j.ajhg.2013.04.003
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/81917
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/81917
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1292622
dc.descriptionProteoglycans (PGs) are a major component of the extracellular matrix in many tissues and function as structural and regulatory molecules. PGs are composed of core proteins and glycosaminoglycan (GAG) side chains. The biosynthesis of GAGs starts with the linker region that consists of four sugar residues and is followed by repeating disaccharide units. By exome sequencing, we found that B3GALT6 encoding an enzyme involved in the biosynthesis of the GAG linker region is responsible for a severe skeletal dysplasia, spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMD-JL1). B3GALT6 loss-of-function mutations were found in individuals with SEMD-JL1 from seven families. In a subsequent candidate gene study based on the phenotypic similarity, we found that B3GALT6 is also responsible for a connective tissue disease, Ehlers-Danlos syndrome (progeroid form). Recessive loss-of-function mutations in B3GALT6 result in a spectrum of disorders affecting a broad range of skeletal and connective tissues characterized by lax skin, muscle hypotonia, joint dislocation, and spinal deformity. The pleiotropic phenotypes of the disorders indicate that B3GALT6 plays a critical role in a wide range of biological processes in various tissues, including skin, bone, cartilage, tendon, and ligament.
dc.description92
dc.description6
dc.description927
dc.description934
dc.descriptionMinistry of Health, Labor, and Welfare [23300101, 23300201]
dc.descriptionJapan Society for the Promotion of Science [23689052, 23790066]
dc.descriptionMatching Program for Innovations in Future Drug Discovery and Medical Care
dc.descriptionMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)
dc.descriptionAkiyama Life Science Foundation
dc.descriptionSwiss National Science Foundation [31003A_141241, 310030_132940]
dc.descriptionCoSMO-B project (Brazil)
dc.descriptionCoSMO-B project (Switzerland)
dc.descriptionLeenaards Foundation (Switzerland)
dc.descriptionResearch on intractable diseases, Health and Labour Sciences Research Grants [H23-Nanchi-Ippan-123]
dc.descriptionMinistry of Health, Labor, and Welfare [23300101, 23300201]
dc.descriptionJapan Society for the Promotion of Science [23689052, 23790066]
dc.descriptionSwiss National Science Foundation [31003A_141241, 310030_132940]
dc.descriptionResearch on intractable diseases, Health and Labour Sciences Research Grants [H23-Nanchi-Ippan-123]
dc.languageen
dc.publisherCell Press
dc.publisherCambridge
dc.publisherEUA
dc.relationAmerican Journal Of Human Genetics
dc.relationAm. J. Hum. Genet.
dc.rightsfechado
dc.sourceWeb of Science
dc.subjectEhlers-danlos-syndrome
dc.subjectJoint Laxity
dc.subjectDysplasia
dc.subjectProteoglycan
dc.subjectBiosynthesis
dc.subjectFibroblasts
dc.subjectPatient
dc.subjectVariant
dc.subjectKif22
dc.subjectGene
dc.titleMutations in B3GALT6, which Encodes a Glycosaminoglycan Linker Region Enzyme, Cause a Spectrum of Skeletal and Connective Tissue Disorders
dc.typeArtículos de revistas


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