2. Academic Validation
  3. BGN Mutations in X-Linked Spondyloepimetaphyseal Dysplasia

BGN Mutations in X-Linked Spondyloepimetaphyseal Dysplasia

  • Am J Hum Genet. 2016 Jun 2;98(6):1243-1248. doi: 10.1016/j.ajhg.2016.04.004.
Sung Yoon Cho 1,  Jun-Seok Bae 2,  Nayoung K D Kim 3,  Francesca Forzano 4,  Katta Mohan Girisha 5,  Chiara Baldo 6,  Francesca Faravelli 4,  Tae-Joon Cho 7,  Dongsup Kim 8,  Kyoung Yeul Lee 8,  Shiro Ikegawa 9,  Jong Sup Shim 10,  Ah-Ra Ko 11,  Noriko Miyake 12,  Gen Nishimura 13,  Andrea Superti-Furga 14,  Jürgen Spranger 15,  Ok-Hwa Kim 16,  Woong-Yang Park 17,  Dong-Kyu Jin 18
Affiliations

Affiliations

  • 1 Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.
  • 2 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.
  • 3 Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.
  • 4 Division of Medical Genetics, Galliera Hospital, Via Volta 6, Genova 16128, Italy.
  • 5 Department of Medical Genetics, Kasturba Medical College, Manipal University, Manipal 576104, India.
  • 6 Laboratory of Human Genetics, Galliera Hospital, Genova 16128, Italy.
  • 7 Division of Pediatric Orthopaedics, Seoul National University Children's Hospital, Seoul 03080, Republic of Korea.
  • 8 Department of Systems Biology, Korea Advanced Institute of Science and Technology, Daejon 34141, Republic of Korea.
  • 9 Laboratory for Bone and Joint Diseases, RIKEN Center for Integrative Medical Sciences, Tokyo 108-8639, Japan.
  • 10 Department of Orthopedic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.
  • 11 Clinical Research Center, Samsung Biomedical Research Center, Seoul 06351, Republic of Korea.
  • 12 Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
  • 13 Department of Pediatric Imaging, Tokyo Metropolitan Children's Medical Center, Fuchu 183-8561, Japan.
  • 14 Department of Pediatrics, Centre Hospitalier Universitaire Vaudois, University of Lausanne (CHUV), Lausanne 1011, Switzerland.
  • 15 Im Fuchsberg 14, 76547 Sinzheim, Germany.
  • 16 Department of Radiology, Woorisoa Children's Hospital, Seoul 08291, Republic of Korea.
  • 17 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.
  • 18 Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea. Electronic address: jindk@skku.edu.
PMID: 27236923 DOI: 10.1016/j.ajhg.2016.04.004
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.

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