BGN Mutations in X-Linked Spondyloepimetaphyseal Dysplasia

Sung Yoon Cho, Jun Seok Bae, Nayoung K.D. Kim, Francesca Forzano, Katta Mohan Girisha, Chiara Baldo, Francesca Faravelli, Tae Joon Cho, Dongsup Kim, Kyoung Yeul Lee, Shiro Ikegawa, Jong Sup Shim, Ah Ra Ko, Noriko Miyake, Gen Nishimura, Andrea Superti-Furga, Jürgen Spranger, Ok Hwa Kim, Woong Yang Park, Dong Kyu Jin

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1243-1248
Number of pages6
JournalAmerican Journal of Human Genetics
Volume98
Issue number6
DOIs
Publication statusPublished - 02-06-2016

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Mutation
Biglycan
Transforming Growth Factor beta
Exome
Missense Mutation
Proteoglycans
Korea
Leucine
Extracellular Matrix
India
Observation
X-Linked Spondyloepimetaphyseal Dysplasia

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

Cite this

Cho, S. Y., Bae, J. S., Kim, N. K. D., Forzano, F., Girisha, K. M., Baldo, C., ... Jin, D. K. (2016). BGN Mutations in X-Linked Spondyloepimetaphyseal Dysplasia. American Journal of Human Genetics, 98(6), 1243-1248. https://doi.org/10.1016/j.ajhg.2016.04.004
Cho, Sung Yoon ; Bae, Jun Seok ; Kim, Nayoung K.D. ; Forzano, Francesca ; Girisha, Katta Mohan ; Baldo, Chiara ; Faravelli, Francesca ; Cho, Tae Joon ; Kim, Dongsup ; Lee, Kyoung Yeul ; Ikegawa, Shiro ; Shim, Jong Sup ; Ko, Ah Ra ; Miyake, Noriko ; Nishimura, Gen ; Superti-Furga, Andrea ; Spranger, Jürgen ; Kim, Ok Hwa ; Park, Woong Yang ; Jin, Dong Kyu. / BGN Mutations in X-Linked Spondyloepimetaphyseal Dysplasia. In: American Journal of Human Genetics. 2016 ; Vol. 98, No. 6. pp. 1243-1248.
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Cho, SY, Bae, JS, Kim, NKD, Forzano, F, Girisha, KM, Baldo, C, Faravelli, F, Cho, TJ, Kim, D, Lee, KY, Ikegawa, S, Shim, JS, Ko, AR, Miyake, N, Nishimura, G, Superti-Furga, A, Spranger, J, Kim, OH, Park, WY & Jin, DK 2016, 'BGN Mutations in X-Linked Spondyloepimetaphyseal Dysplasia', American Journal of Human Genetics, vol. 98, no. 6, pp. 1243-1248. https://doi.org/10.1016/j.ajhg.2016.04.004

BGN Mutations in X-Linked Spondyloepimetaphyseal Dysplasia. / Cho, Sung Yoon; Bae, Jun Seok; Kim, Nayoung K.D.; Forzano, Francesca; Girisha, Katta Mohan; Baldo, Chiara; Faravelli, Francesca; Cho, Tae Joon; Kim, Dongsup; Lee, Kyoung Yeul; Ikegawa, Shiro; Shim, Jong Sup; Ko, Ah Ra; Miyake, Noriko; Nishimura, Gen; Superti-Furga, Andrea; Spranger, Jürgen; Kim, Ok Hwa; Park, Woong Yang; Jin, Dong Kyu.

In: American Journal of Human Genetics, Vol. 98, No. 6, 02.06.2016, p. 1243-1248.

Research output: Contribution to journalArticle

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T1 - BGN Mutations in X-Linked Spondyloepimetaphyseal Dysplasia

AU - Cho, Sung Yoon

AU - Bae, Jun Seok

AU - Kim, Nayoung K.D.

AU - Forzano, Francesca

AU - Girisha, Katta Mohan

AU - Baldo, Chiara

AU - Faravelli, Francesca

AU - Cho, Tae Joon

AU - Kim, Dongsup

AU - Lee, Kyoung Yeul

AU - Ikegawa, Shiro

AU - Shim, Jong Sup

AU - Ko, Ah Ra

AU - Miyake, Noriko

AU - Nishimura, Gen

AU - Superti-Furga, Andrea

AU - Spranger, Jürgen

AU - Kim, Ok Hwa

AU - Park, Woong Yang

AU - Jin, Dong Kyu

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Y1 - 2016/6/2

N2 - 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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