title: BGN Mutations in X-Linked Spondyloepimetaphyseal Dysplasia.
abstract: Spondyloepimetaphyseal dysplasias (SEMDs) comprise a heterogeneous group of autosomal-dominant and autosomal-recessive disorders. An apparent X-linked recessive (XLR) form of SEMD in a single Italian family was previously reported. We have been able to restudy this family together with a second family from Korea by segregating a severe SEMD in an X-linked pattern. Exome sequencing showed missense mutations in BGN c.439A>G (p.Lys147Glu) in the Korean family and c.776G>T (p.Gly259Val) in the Italian family; the c.439A>G (p.Lys147Glu) mutation was also identified in a further simplex SEMD case from India. Biglycan is an extracellular matrix proteoglycan that can bind transforming growth factor beta (TGF-β) and thus regulate its free concentration. In 3-dimensional simulation, both altered residues localized to the concave arc of leucine-rich repeat domains of biglycan that interact with TGF-β. The observation of recurrent BGN mutations in XLR SEMD individuals from different ethnic backgrounds allows us to define "XLR SEMD, BGN type" as a nosologic entity.
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.
authors.forename: Sung Yoon
authors.initials: SY
authors.lastname: Cho
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.
authors.forename: Jun-Seok
authors.initials: JS
authors.lastname: Bae
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.
authors.forename: Nayoung K D
authors.initials: NKD
authors.lastname: Kim
authors.affiliation: Division of Medical Genetics, Galliera Hospital, Via Volta 6, Genova 16128, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Forzano
authors.affiliation: Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal 576104, India.
authors.forename: Katta Mohan
authors.initials: KM
authors.lastname: Girisha
authors.affiliation: Laboratory of Human Genetics, Galliera Hospital, Genova 16128, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Baldo
authors.affiliation: Division of Medical Genetics, Galliera Hospital, Via Volta 6, Genova 16128, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Faravelli
authors.affiliation: Division of Pediatric Orthopaedics, Seoul National University Children's Hospital, Seoul 03080, Republic of Korea.
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Cho
authors.affiliation: Department of Systems Biology, Korea Advanced Institute of Science and Technology, Daejon 34141, Republic of Korea.
authors.forename: Dongsup
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Systems Biology, Korea Advanced Institute of Science and Technology, Daejon 34141, Republic of Korea.
authors.forename: Kyoung Yeul
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo 108-8639, Japan.
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
authors.affiliation: Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.
authors.forename: Jong Sup
authors.initials: JS
authors.lastname: Shim
authors.affiliation: Clinical Research Center, Samsung Biomedical Research Center, Seoul 06351, Republic of Korea.
authors.forename: Ah-Ra
authors.initials: AR
authors.lastname: Ko
authors.affiliation: Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.affiliation: Department of Pediatric Imaging, Tokyo Metropolitan Children's Medical Center, Fuchu 183-8561, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Nishimura
authors.affiliation: Department of Pediatrics, Centre Hospitalier Universitaire Vaudois, University of Lausanne (CHUV), Lausanne 1011, Switzerland.
authors.forename: Andrea
authors.initials: A
authors.lastname: Superti-Furga
authors.affiliation: Im Fuchsberg 14, 76547 Sinzheim, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Spranger
authors.affiliation: Department of Radiology, Woorisoa Children's Hospital, Seoul 08291, Republic of Korea.
authors.forename: Ok-Hwa
authors.initials: OH
authors.lastname: Kim
authors.affiliation: Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea; Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea. Electronic address: woongyang.park@samsung.com.
authors.forename: Woong-Yang
authors.initials: WY
authors.lastname: Park
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea. Electronic address: jindk@skku.edu.
authors.forename: Dong-Kyu
authors.initials: DK
authors.lastname: Jin
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D058578:Biglycan / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000235:genetics*; D010375:Pedigree; D011485:Protein Binding; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D016212:Transforming Growth Factor beta / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: C546884:BGN protein, human; D058578:Biglycan; D016212:Transforming Growth Factor beta