BGN Mutations in X-Linked Spondyloepimetaphyseal Dysplasia

被引：37

作者：

Cho, Sung Yoon ^{[1
]}

Bae, Jun-Seok ^{[2
,3
]}

Kim, Nayoung K. D. ^{[2
]}

Forzano, Francesca ^{[4
]}

Girisha, Katta Mohan ^{[5
]}

Baldo, Chiara ^{[6
]}

Faravelli, Francesca ^{[4
]}

Cho, Tae-Joon ^{[7
]}

Kim, Dongsup ^{[8
]}

Lee, Kyoung Yeul ^{[8
]}

Ikegawa, Shiro ^{[9
]}

Shim, Jong Sup ^{[10
]}

Ko, Ah-Ra ^{[11
]}

Miyake, Noriko ^{[12
]}

Nishimura, Gen ^{[13
]}

Superti-Furga, Andrea ^{[14
]}

Spranger, Juergen ^{[15
]}

Kim, Ok-Hwa ^{[16
]}

Park, Woong-Yang ^{[2
,3
,17
]}

Jin, Dong-Kyu ^{[1
]}

机构：

[1] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pediat, Seoul 06351, South Korea

[2] Sungkyunkwan Univ, Samsung Med Ctr, Sch Med, Samsung Genome Inst, Seoul 06351, South Korea

[3] Sungkyunkwan Univ, Samsung Adv Inst Hlth Sci & Technol, Samsung Med Ctr, Dept Hlth Sci & Technol,Sch Med, Seoul 06351, South Korea

[4] Galliera Hosp, Div Med Genet, Via Volta 6, I-16128 Genoa, Italy

[5] Manipal Univ, Kasturba Med Coll, Dept Med Genet, Manipal 576104, Karnataka, India

[6] Galliera Hosp, Lab Human Genet, I-16128 Genoa, Italy

[7] Seoul Natl Univ, Childrens Hosp, Div Pediat Orthopaed, Seoul 03080, South Korea

[8] Korea Adv Inst Sci & Technol, Dept Syst Biol, Daejon 34141, South Korea

[9] RIKEN, Ctr Integrat Med Sci, Lab Bone & Joint Dis, Tokyo 1088639, Japan

[10] Sungkyunkwan Univ, Samsung Med Ctr, Sch Med, Dept Orthoped Surg, Seoul 06351, South Korea

[11] Samsung Biomed Res Ctr, Clin Res Ctr, Seoul 06351, South Korea

[12] Yokohama City Univ, Grad Sch Med, Dept Human Genet, Yokohama, Kanagawa 2360004, Japan

[13] Tokyo Metropolitan Childrens Med Ctr, Dept Pediat Imaging, Fuchu, Tokyo 1838561, Japan

[14] Univ Lausanne, CHUV, Dept Pediat, CH-1011 Lausanne, Switzerland

[15] Fuchsberg 14, D-76547 Sinzheim, Germany

[16] Woorisoa Childrens Hosp, Dept Radiol, Seoul 08291, South Korea

[17] Sungkyunkwan Univ, Sch Med, Dept Mol Cell Biol, Suwon 16419, South Korea

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2016年 / 98卷 / 06期

关键词：

OSTEOBLAST DIFFERENTIATION; EXTRACELLULAR-MATRIX; PROTEOGLYCANS BIGLYCAN; DISEASES; MICE; OSTEOPOROSIS; EXPRESSION; PATHWAYS; DECORIN; MODELS;

D O I：

10.1016/j.ajhg.2016.04.004

中图分类号：

Q3 [遗传学];

学科分类号：

071007 [遗传学];

摘要：

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-beta) 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-beta. 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.

引用

页码：1243 / 1248

页数：6

共 15 条

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Mice deficient in small leucine-rich proteoglycans:: novel in vivo models for osteoporosis, osteoarthritis, Ehlers-Danlos syndrome, muscular dystrophy, and corneal diseases [J].