BROWSE

Related Researcher

Author's Photo

Myung, Kyungjae
Center for Genomic Integrity
Research Interests
  • DNA Replication, DNA Repair, DNA Recombination, DNA Damage Response, cancer, aging

ITEM VIEW & DOWNLOAD

Hypomorphic Mutations in TONSL Cause SPONASTRIME Dysplasia

Cited 0 times inthomson ciCited 0 times inthomson ci
Title
Hypomorphic Mutations in TONSL Cause SPONASTRIME Dysplasia
Author
Chang, Hae RyungCho, Sung YoonLee, Jae HoonLee, EunkyungSeo, JieunLee, Hye RanCavalcanti, Denise P.Makitie, OutiValta, HelenaGirisha, Katta M.Lee, ChungNeethukrishna, KausthubhamBhavani, Gandham S.Shukla, AnjuNampoothiri, SheelaPhadkei, Shubha R.Park, Mi JungIkegawa, ShiroWang, ZhengHiggs, Martin R.Stewart, Grant S.Jung, EunyoungLee, Myeong-SokPark, Jong HoonLee, Eun A.Kim, HongtaeMyung, KyungjaeJeon, WoosungLee, KyoungyeulKim, DongsupKim, Ok-HwaChoi, MurimLee, Han-WoongKim, YonghwanCho, Tae-Joon
Issue Date
2019-03
Publisher
CELL PRESS
Citation
AMERICAN JOURNAL OF HUMAN GENETICS, v.104, no.3, pp.439 - 453
Abstract
SPONASTRIME dysplasia is a rare, recessive skeletal dysplasia characterized by short stature, facial dysmorphism, and aberrant radiographic findings of the spine and long bone metaphysis. No causative genetic alterations for SPONASTRIME dysplasia have yet been determined. Using whole-exome sequencing (WES), we identified bi-allelic TONSL mutations in 10 of 13 individuals with SPONASTRIME dysplasia. TONSL is a multi-domain scaffold protein that interacts with DNA replication and repair factors and which plays critical roles in resistance to replication stress and the maintenance of genome integrity. We show here that cellular defects in dermal fibroblasts from affected individuals are complemented by the expression of wild-type TONSL. In addition, in vitro cell-based as-says and in silico analyses of TONSL structure support the pathogenicity of those TONSL variants. Intriguingly, a knock-in (KI) Tonsl mouse model leads to embryonic lethality, implying the physiological importance of TONSL. Overall, these findings indicate that genetic variants resulting in reduced function of TONSL cause SPONASTRIME dysplasia and highlight the importance of TONSL in embryonic development and postnatal growth.
URI
https://scholarworks.unist.ac.kr/handle/201301/30506
URL
https://www.sciencedirect.com/science/article/pii/S0002929719300096?via%3Dihub
DOI
10.1016/j.ajhg.2019.01.009
ISSN
0002-9297
Appears in Collections:
SLS_Journal Papers
Files in This Item:
There are no files associated with this item.

find_unist can give you direct access to the published full text of this article. (UNISTARs only)

Show full item record

qrcode

  • mendeley

    citeulike

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

MENU