Osteogenesis imperfecta(OI)is mainly characterized by bone fragility and Ehlers-Danlos syndrome(EDS)by connective tissue defects.Mutations in COL1A1 or COL1A2 can lead to both syndromes.OI/EDS overlap syndrome is most...Osteogenesis imperfecta(OI)is mainly characterized by bone fragility and Ehlers-Danlos syndrome(EDS)by connective tissue defects.Mutations in COL1A1 or COL1A2 can lead to both syndromes.OI/EDS overlap syndrome is mostly caused by helical mutations near the amino-proteinase cleavage site of type Ⅰ procollagen.In this study,we identified a Thai patient having OI type Ⅲ,EDS,brachydactyly,and dentinogenesis imperfecta.His dentition showed delayed eruption,early exfoliation,and severe malocclusion.For the first time,ultrastructural analysis of the tooth affected with OI/EDS showed that the tooth had enamel inversion,bonelike dentin,loss of dentinal tubules,and reduction in hardness and elasticity,suggesting severe developmental disturbance.These severe dental defects have never been reported in OI or EDS.Exome sequencing identified a novel de novo heterozygous glycine substitution,c.3296G>A,p.Gly1099Glu,in exon 49 of COL1A2.Three patients with mutations in the exon 49 of COL1A2 were previously reported to have OI with brachydactyly and intracranial hemorrhage.Notably,two of these three patients did not show hyperextensible joints and hypermobile skin,while our patient at the age of 5 years had not developed intracranial hemorrhage.Here,we demonstrate that the novel glycine substitution in the carboxyl region of alpha2(Ⅰ)collagen triple helix leads to OI/EDS with brachydactyly and severe tooth defects,expanding the genotypic and phenotypic spectra of OI/EDS overlap syndrome.展开更多
基金supported by the 90th Anniversary of Chulalongkorn University,Rachadapisek Sompote FundFaculty of Dentistry(DFR62003),Chulalongkorn University+3 种基金Chulalongkorn Academic Advancement Into Its 2nd Century ProjectNewton FundThailand Research Fund(RSA6280001,DPG6180001)supported by Ratchadapisek Somphot Fund for Postdoctoral Fellowship,Chulalongkorn University,Thailand。
文摘Osteogenesis imperfecta(OI)is mainly characterized by bone fragility and Ehlers-Danlos syndrome(EDS)by connective tissue defects.Mutations in COL1A1 or COL1A2 can lead to both syndromes.OI/EDS overlap syndrome is mostly caused by helical mutations near the amino-proteinase cleavage site of type Ⅰ procollagen.In this study,we identified a Thai patient having OI type Ⅲ,EDS,brachydactyly,and dentinogenesis imperfecta.His dentition showed delayed eruption,early exfoliation,and severe malocclusion.For the first time,ultrastructural analysis of the tooth affected with OI/EDS showed that the tooth had enamel inversion,bonelike dentin,loss of dentinal tubules,and reduction in hardness and elasticity,suggesting severe developmental disturbance.These severe dental defects have never been reported in OI or EDS.Exome sequencing identified a novel de novo heterozygous glycine substitution,c.3296G>A,p.Gly1099Glu,in exon 49 of COL1A2.Three patients with mutations in the exon 49 of COL1A2 were previously reported to have OI with brachydactyly and intracranial hemorrhage.Notably,two of these three patients did not show hyperextensible joints and hypermobile skin,while our patient at the age of 5 years had not developed intracranial hemorrhage.Here,we demonstrate that the novel glycine substitution in the carboxyl region of alpha2(Ⅰ)collagen triple helix leads to OI/EDS with brachydactyly and severe tooth defects,expanding the genotypic and phenotypic spectra of OI/EDS overlap syndrome.
