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Article: Mutations in the Heparan-Sulfate Proteoglycan Glypican 6 (GPC6) Impair Endochondral Ossification and Cause Recessive Omodysplasia

TitleMutations in the Heparan-Sulfate Proteoglycan Glypican 6 (GPC6) Impair Endochondral Ossification and Cause Recessive Omodysplasia
Authors
Issue Date2009
PublisherCell Press. The Journal's web site is located at http://www.cell.com/AJHG/
Citation
American Journal Of Human Genetics, 2009, v. 84 n. 6, p. 760-770 How to Cite?
AbstractGlypicans are a family of glycosylphosphatidylinositol (GPI)-anchored, membrane-bound heparan sulfate (HS) proteoglycans. Their biological roles are only partly understood, although it is assumed that they modulate the activity of HS-binding growth factors. The involvement of glypicans in developmental morphogenesis and growth regulation has been highlighted by Drosophila mutants and by a human overgrowth syndrome with multiple malformations caused by glypican 3 mutations (Simpson-Golabi-Behmel syndrome). We now report that autosomal-recessive omodysplasia, a genetic condition characterized by short-limbed short stature, craniofacial dysmorphism, and variable developmental delay, maps to chromosome 13 (13q31.1-q32.2) and is caused by point mutations or by larger genomic rearrangements in glypican 6 (GPC6). All mutations cause truncation of the GPC6 protein and abolish both the HS-binding site and the GPI-bearing membrane-associated domain, and thus loss of function is predicted. Expression studies in microdissected mouse growth plate revealed expression of Gpc6 in proliferative chondrocytes. Thus, GPC6 seems to have a previously unsuspected role in endochondral ossification and skeletal growth, and its functional abrogation results in a short-limb phenotype. © 2009 The American Society of Human Genetics.
Persistent Identifierhttp://hdl.handle.net/10722/170413
ISSN
2015 Impact Factor: 10.794
2015 SCImago Journal Rankings: 8.769
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorCamposXavier, ABen_US
dc.contributor.authorMartinet, Den_US
dc.contributor.authorBateman, Jen_US
dc.contributor.authorBelluoccio, Den_US
dc.contributor.authorRowley, Len_US
dc.contributor.authorTan, TYen_US
dc.contributor.authorBaxová, Aen_US
dc.contributor.authorGustavson, KHen_US
dc.contributor.authorBorochowitz, ZUen_US
dc.contributor.authorInnes, AMen_US
dc.contributor.authorUnger, Sen_US
dc.contributor.authorBeckmann, JSen_US
dc.contributor.authorMittaz, Len_US
dc.contributor.authorBallhausen, Den_US
dc.contributor.authorSupertiFurga, Aen_US
dc.contributor.authorSavarirayan, Ren_US
dc.contributor.authorBonafé, Len_US
dc.date.accessioned2012-10-30T06:08:18Z-
dc.date.available2012-10-30T06:08:18Z-
dc.date.issued2009en_US
dc.identifier.citationAmerican Journal Of Human Genetics, 2009, v. 84 n. 6, p. 760-770en_US
dc.identifier.issn0002-9297en_US
dc.identifier.urihttp://hdl.handle.net/10722/170413-
dc.description.abstractGlypicans are a family of glycosylphosphatidylinositol (GPI)-anchored, membrane-bound heparan sulfate (HS) proteoglycans. Their biological roles are only partly understood, although it is assumed that they modulate the activity of HS-binding growth factors. The involvement of glypicans in developmental morphogenesis and growth regulation has been highlighted by Drosophila mutants and by a human overgrowth syndrome with multiple malformations caused by glypican 3 mutations (Simpson-Golabi-Behmel syndrome). We now report that autosomal-recessive omodysplasia, a genetic condition characterized by short-limbed short stature, craniofacial dysmorphism, and variable developmental delay, maps to chromosome 13 (13q31.1-q32.2) and is caused by point mutations or by larger genomic rearrangements in glypican 6 (GPC6). All mutations cause truncation of the GPC6 protein and abolish both the HS-binding site and the GPI-bearing membrane-associated domain, and thus loss of function is predicted. Expression studies in microdissected mouse growth plate revealed expression of Gpc6 in proliferative chondrocytes. Thus, GPC6 seems to have a previously unsuspected role in endochondral ossification and skeletal growth, and its functional abrogation results in a short-limb phenotype. © 2009 The American Society of Human Genetics.en_US
dc.languageengen_US
dc.publisherCell Press. The Journal's web site is located at http://www.cell.com/AJHG/en_US
dc.relation.ispartofAmerican Journal of Human Geneticsen_US
dc.subject.meshAbnormalities, Multiple - Geneticsen_US
dc.subject.meshAnimalsen_US
dc.subject.meshChild, Preschoolen_US
dc.subject.meshChondrocytes - Metabolismen_US
dc.subject.meshChromosome Mappingen_US
dc.subject.meshChromosomes, Human, Pair 13 - Geneticsen_US
dc.subject.meshComparative Genomic Hybridizationen_US
dc.subject.meshDwarfism - Geneticsen_US
dc.subject.meshFemaleen_US
dc.subject.meshFluorescent Antibody Techniqueen_US
dc.subject.meshGenes, Recessive - Geneticsen_US
dc.subject.meshGlypicans - Geneticsen_US
dc.subject.meshHumansen_US
dc.subject.meshInfanten_US
dc.subject.meshInfant, Newbornen_US
dc.subject.meshMaleen_US
dc.subject.meshMiceen_US
dc.subject.meshMutation - Geneticsen_US
dc.subject.meshOsteogenesis - Physiologyen_US
dc.titleMutations in the Heparan-Sulfate Proteoglycan Glypican 6 (GPC6) Impair Endochondral Ossification and Cause Recessive Omodysplasiaen_US
dc.typeArticleen_US
dc.identifier.emailTan, TY:tanty@hku.hken_US
dc.identifier.authorityTan, TY=rp01380en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1016/j.ajhg.2009.05.002en_US
dc.identifier.pmid19481194-
dc.identifier.scopuseid_2-s2.0-66449083531en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-66449083531&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume84en_US
dc.identifier.issue6en_US
dc.identifier.spage760en_US
dc.identifier.epage770en_US
dc.identifier.isiWOS:000267042800006-
dc.publisher.placeUnited Statesen_US
dc.identifier.f10001161851-
dc.identifier.scopusauthoridCamposXavier, AB=6506768052en_US
dc.identifier.scopusauthoridMartinet, D=13613374300en_US
dc.identifier.scopusauthoridBateman, J=16135557700en_US
dc.identifier.scopusauthoridBelluoccio, D=27367471200en_US
dc.identifier.scopusauthoridRowley, L=24173785000en_US
dc.identifier.scopusauthoridTan, TY=8567188100en_US
dc.identifier.scopusauthoridBaxová, A=6602535976en_US
dc.identifier.scopusauthoridGustavson, KH=7103138225en_US
dc.identifier.scopusauthoridBorochowitz, ZU=7004733530en_US
dc.identifier.scopusauthoridInnes, AM=7006028491en_US
dc.identifier.scopusauthoridUnger, S=7102821012en_US
dc.identifier.scopusauthoridBeckmann, JS=7101802107en_US
dc.identifier.scopusauthoridMittaz, L=7801520439en_US
dc.identifier.scopusauthoridBallhausen, D=6505851396en_US
dc.identifier.scopusauthoridSupertiFurga, A=7006588536en_US
dc.identifier.scopusauthoridSavarirayan, R=7003566196en_US
dc.identifier.scopusauthoridBonafé, L=6701522243en_US
dc.identifier.citeulike4939462-

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