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Am J Hum Genet. 2016 Jun 2;98(6):1243-1248. doi: 10.1016/j.ajhg.2016.04.004. Epub 2016 May 26.

BGN Mutations in X-Linked Spondyloepimetaphyseal Dysplasia.

Author information

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.

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.

PMID:
27236923
PMCID:
PMC4908150
DOI:
10.1016/j.ajhg.2016.04.004
[Indexed for MEDLINE]
Free PMC Article

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