Novel loss-of-function variants of TRAPPC2 manifesting X-linked spondyloepiphyseal dysplasia tarda: Report of two cases

Joon Yeon Won; Dayeon Kim; Seon Young Park; Hye Ran Lee; Jong Seok Lim; Jong Hoon Park; Mi Hyun Song; Hae Ryong Song; Ok Hwa Kim; Yonghwan Kim; Tae Joon Cho

doi:10.1186/s12881-019-0802-2

Novel loss-of-function variants of TRAPPC2 manifesting X-linked spondyloepiphyseal dysplasia tarda: Report of two cases

Joon Yeon Won
, Dayeon Kim
, Seon Young Park
, Hye Ran Lee
, Jong Seok Lim
, Jong Hoon Park
, Mi Hyun Song
, Hae Ryong Song
, Ok Hwa Kim
, Yonghwan Kim^*
, Tae Joon Cho

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

Abstract

Background: X-linked spondyloepiphyseal dysplasia tarda (SEDT-XL) is a skeletal disorder characterized by defective structures of vertebral bodies and/or of epiphyses of the long bones, resulting in moderately short stature and early joint degeneration. TRAPPC2 gene, which is important for collagen secretion, has been reported as causative for SEDT-XL. Case presentation: Here, we report two variants of TRAPPC2 gene of SEDT-XL patients, a missense variant of start codon, c.1A > T, and a deletion variant, c.40delG. To understand molecular consequence of the variants, we establish an in vitro gene expression assay system and demonstrate that both mutated genes are transcribed, but are not properly translated, indicative of the pathogenic nature of those TRAPPC2 variants. Conclusions: In the current study, we provide additional experimental data showing that loss-of-function TRAPPC2 variants are probably causative for SEDT-XL phenotype. These findings further contribute to the understanding the clinical picture related to TRAPPC2 gene.

Original language	English
Article number	70
Journal	BMC Medical Genetics
Volume	20
Issue number	1
DOIs	https://doi.org/10.1186/s12881-019-0802-2
Publication status	Published - 2019 May 3

Bibliographical note

Funding Information:
TJC is supported by National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning of the Korean government (NRF-2014M3C9A2064684: Genome Technology to Business Translation Program), which has been used for the patient recruitment and care, and determining genetic variants. YK is supported by NRF funded by the Ministry of Science, ICT & Future Planning of the Korean government (NRF-2014M3C9A2064688: Genome Technology to Business Translation Program and NRF-2016R1A5A1011974), which have been used for validation of the pathogenicity of identified variants and in vitro functional studies. All the decisions regarding to the current studies are made by authors, not by funders. The funders are not involved in the study design, data collection and analysis, performing experiments and in writing the manuscript.

Publisher Copyright:
© 2019 The Author(s).

Keywords

Gene expression
Skeletal dysplasia
TRAPPC2
X-linked spondyloepiphyseal dysplasia tarda

ASJC Scopus subject areas

Genetics
Genetics(clinical)

Access to Document

10.1186/s12881-019-0802-2

Cite this

@article{3dd2522dbbd1468592a089c520ff36a6,

title = "Novel loss-of-function variants of TRAPPC2 manifesting X-linked spondyloepiphyseal dysplasia tarda: Report of two cases",

abstract = "Background: X-linked spondyloepiphyseal dysplasia tarda (SEDT-XL) is a skeletal disorder characterized by defective structures of vertebral bodies and/or of epiphyses of the long bones, resulting in moderately short stature and early joint degeneration. TRAPPC2 gene, which is important for collagen secretion, has been reported as causative for SEDT-XL. Case presentation: Here, we report two variants of TRAPPC2 gene of SEDT-XL patients, a missense variant of start codon, c.1A > T, and a deletion variant, c.40delG. To understand molecular consequence of the variants, we establish an in vitro gene expression assay system and demonstrate that both mutated genes are transcribed, but are not properly translated, indicative of the pathogenic nature of those TRAPPC2 variants. Conclusions: In the current study, we provide additional experimental data showing that loss-of-function TRAPPC2 variants are probably causative for SEDT-XL phenotype. These findings further contribute to the understanding the clinical picture related to TRAPPC2 gene.",

keywords = "Gene expression, Skeletal dysplasia, TRAPPC2, X-linked spondyloepiphyseal dysplasia tarda",

author = "Won, \{Joon Yeon\} and Dayeon Kim and Park, \{Seon Young\} and Lee, \{Hye Ran\} and Lim, \{Jong Seok\} and Park, \{Jong Hoon\} and Song, \{Mi Hyun\} and Song, \{Hae Ryong\} and Kim, \{Ok Hwa\} and Yonghwan Kim and Cho, \{Tae Joon\}",

note = "Funding Information: TJC is supported by National Research Foundation (NRF) funded by the Ministry of Science, ICT \& Future Planning of the Korean government (NRF-2014M3C9A2064684: Genome Technology to Business Translation Program), which has been used for the patient recruitment and care, and determining genetic variants. YK is supported by NRF funded by the Ministry of Science, ICT \& Future Planning of the Korean government (NRF-2014M3C9A2064688: Genome Technology to Business Translation Program and NRF-2016R1A5A1011974), which have been used for validation of the pathogenicity of identified variants and in vitro functional studies. All the decisions regarding to the current studies are made by authors, not by funders. The funders are not involved in the study design, data collection and analysis, performing experiments and in writing the manuscript. Publisher Copyright: {\textcopyright} 2019 The Author(s).",

year = "2019",

month = may,

day = "3",

doi = "10.1186/s12881-019-0802-2",

language = "English",

volume = "20",

journal = "BMC Medical Genetics",

issn = "1471-2350",

publisher = "BioMed Central",

number = "1",

}

TY - JOUR

T1 - Novel loss-of-function variants of TRAPPC2 manifesting X-linked spondyloepiphyseal dysplasia tarda

T2 - Report of two cases

AU - Won, Joon Yeon

AU - Kim, Dayeon

AU - Park, Seon Young

AU - Lee, Hye Ran

AU - Lim, Jong Seok

AU - Park, Jong Hoon

AU - Song, Mi Hyun

AU - Song, Hae Ryong

AU - Kim, Ok Hwa

AU - Kim, Yonghwan

AU - Cho, Tae Joon

N1 - Funding Information: TJC is supported by National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning of the Korean government (NRF-2014M3C9A2064684: Genome Technology to Business Translation Program), which has been used for the patient recruitment and care, and determining genetic variants. YK is supported by NRF funded by the Ministry of Science, ICT & Future Planning of the Korean government (NRF-2014M3C9A2064688: Genome Technology to Business Translation Program and NRF-2016R1A5A1011974), which have been used for validation of the pathogenicity of identified variants and in vitro functional studies. All the decisions regarding to the current studies are made by authors, not by funders. The funders are not involved in the study design, data collection and analysis, performing experiments and in writing the manuscript. Publisher Copyright: © 2019 The Author(s).

PY - 2019/5/3

Y1 - 2019/5/3

N2 - Background: X-linked spondyloepiphyseal dysplasia tarda (SEDT-XL) is a skeletal disorder characterized by defective structures of vertebral bodies and/or of epiphyses of the long bones, resulting in moderately short stature and early joint degeneration. TRAPPC2 gene, which is important for collagen secretion, has been reported as causative for SEDT-XL. Case presentation: Here, we report two variants of TRAPPC2 gene of SEDT-XL patients, a missense variant of start codon, c.1A > T, and a deletion variant, c.40delG. To understand molecular consequence of the variants, we establish an in vitro gene expression assay system and demonstrate that both mutated genes are transcribed, but are not properly translated, indicative of the pathogenic nature of those TRAPPC2 variants. Conclusions: In the current study, we provide additional experimental data showing that loss-of-function TRAPPC2 variants are probably causative for SEDT-XL phenotype. These findings further contribute to the understanding the clinical picture related to TRAPPC2 gene.

AB - Background: X-linked spondyloepiphyseal dysplasia tarda (SEDT-XL) is a skeletal disorder characterized by defective structures of vertebral bodies and/or of epiphyses of the long bones, resulting in moderately short stature and early joint degeneration. TRAPPC2 gene, which is important for collagen secretion, has been reported as causative for SEDT-XL. Case presentation: Here, we report two variants of TRAPPC2 gene of SEDT-XL patients, a missense variant of start codon, c.1A > T, and a deletion variant, c.40delG. To understand molecular consequence of the variants, we establish an in vitro gene expression assay system and demonstrate that both mutated genes are transcribed, but are not properly translated, indicative of the pathogenic nature of those TRAPPC2 variants. Conclusions: In the current study, we provide additional experimental data showing that loss-of-function TRAPPC2 variants are probably causative for SEDT-XL phenotype. These findings further contribute to the understanding the clinical picture related to TRAPPC2 gene.

KW - Gene expression

KW - Skeletal dysplasia

KW - TRAPPC2

KW - X-linked spondyloepiphyseal dysplasia tarda

UR - https://www.scopus.com/pages/publications/85065257443

U2 - 10.1186/s12881-019-0802-2

DO - 10.1186/s12881-019-0802-2

M3 - Article

C2 - 31053099

AN - SCOPUS:85065257443

SN - 1471-2350

VL - 20

JO - BMC Medical Genetics

JF - BMC Medical Genetics

IS - 1

M1 - 70

ER -

Novel loss-of-function variants of TRAPPC2 manifesting X-linked spondyloepiphyseal dysplasia tarda: Report of two cases

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this